Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs

Author(s): Ota Fuchs*.

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets

Volume 19 , Issue 1 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) form the family of immunomodulatory drugs (IMiDs). Lenalidomide (CC5013, Revlimid®) was approved by the US FDA and the EMA for the treatment of multiple myeloma (MM) patients, low or intermediate-1 risk transfusion-dependent myelodysplastic syndrome (MDS) with chromosome 5q deletion [del(5q)] and relapsed and/or refractory mantle cell lymphoma following bortezomib. Lenalidomide has also been studied in clinical trials and has shown promising activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Lenalidomide has anti-inflammatory effects and inhibits angiogenesis. Pomalidomide (CC4047, Imnovid® [EU], Pomalyst® [USA]) was approved for advanced MM insensitive to bortezomib and lenalidomide. Other IMiDs are in phases 1 and 2 of clinical trials. Cereblon (CRBN) seems to have an important role in IMiDs action in both lymphoid and myeloid hematological malignancies. Cereblon acts as the substrate receptor of a cullin-4 really interesting new gene (RING) E3 ubiquitin ligase CRL4CRBN. This E3 ubiquitin ligase in the absence of lenalidomide ubiquitinates CRBN itself and the other components of CRL4CRBN complex. Presence of lenalidomide changes specificity of CRL4CRBN which ubiquitinates two transcription factors, IKZF1 (Ikaros) and IKZF3 (Aiolos), and casein kinase 1α (CK1α) and marks them for degradation in proteasomes. Both these transcription factors (IKZF1 and IKZF3) stimulate proliferation of MM cells and inhibit T cells. Low CRBN level was connected with insensitivity of MM cells to lenalidomide. Lenalidomide decreases expression of protein argonaute-2, which binds to cereblon. Argonaute-2 seems to be an important drug target against IMiDs resistance in MM cells. Lenalidomide decreases also basigin and monocarboxylate transporter 1 in MM cells. MM cells with low expression of Ikaros, Aiolos and basigin are more sensitive to lenalidomide treatment. The CK1α gene (CSNK1A1) is located on 5q32 in commonly deleted region (CDR) in del(5q) MDS. Inhibition of CK1α sensitizes del(5q) MDS cells to lenalidomide. CK1α mediates also survival of malignant plasma cells in MM. Though, inhibition of CK1α is a potential novel therapy not only in del(5q) MDS but also in MM. High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide. While transfusion independence (TI) after lenalidomide treatment is more than 60% in MDS patients with del(5q), only 25% TI and substantially shorter duration of response with occurrence of neutropenia and thrombocytopenia were achieved in lower risk MDS patients with normal karyotype treated with lenalidomide. Shortage of the biomarkers for lenalidomide response in these MDS patients is the main problem up to now.

Keywords: Cereblon, casein kinase 1α1, cullin 4-containing RING E3 ubiquitin ligase complex, Ikaros family, immunomodulatory drugs, lenalidomide, pomalidomide, multiple myeloma, del(5q) MDS, mantle lymphoma, proteasome.

[1]
Kunz, W.; Keller, H.; Muckter, H. N-phthalyl-glutamic acid imide; experimental studies on a new synthetic product with sedative properties. Arzneimittelforschung, 1956, 6, 426-430.
[2]
McBride, W.G. Thalidomide and congenital abnormalities. Lancet, 1961, 2, 1358.
[3]
Miller, M.T.; Stromland, K. Teratogen update: Thalidomide: A review with a focus on ocular findings and new potential uses. Teratology, 1999, 60, 306-321.
[4]
Knobloch, J.; Ruther, U. Shedding light on an old mystery: Thalidomide suppresses survival pathways to induce limb defects. Cell Cycle, 2008, 7, 1121-1127.
[5]
Kim, J.H.; Scialli, A.R. Thalidomide: The tragedy of birth defects and the effective treatment of disease. Toxicol. Sci., 2011, 122, 1-6.
[6]
Ito, T.; Handa, H. Deciphering the mystery of thalidomide teratogenicity. Congenit. Anom. (Kyoto), 2012, 52, 1-7. [Kyoto].
[7]
Singhal, S.; Mehta, J.; Desikan, R.; Ayers, D.; Roberson, P.; Eddlemon, P.; Munshi, N.; Anaissie, E.; Wilson, C.; Dhodapkar, M.; Zeddis, J.; Barlogie, B. Antitumor activity of thalidomide in refractory multiple myeloma. N. Engl. J. Med., 1999, 341, 1565-1571.
[8]
Richardson, P.; Anderson, K. Thalidomide and dexamethasone: a new standard of care for initial therapy in multiple myeloma. J. Clin. Oncol., 2006, 24, 334-336.
[9]
Xu, M.; Hou, Y.; Sheng, L.; Peng, J. Therapeutic effects of thalidomide in haematological disorders: A review. Front. Med., 2013, 7, 290-300.
[10]
Mark, T.M.; Bowman, I.A.; Rossi, A.C.; Shah, M.; Rodriguez, M.; Quinn, R.; Pearse, R.N.; Zafar, F.; Pekle, K.; Jayabalan, D.; Ely, S.; Coleman, M.; Chen-Kiang, S.; Niesvizky, R. Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma. Leuk. Lymphoma, 2014, 55, 2842-2849.
[11]
Schey, S.; Brown, S.R.; Tillotson, A.L.; Yong, K.; Williams, C.; Davies, F.; Morgan, G.; Cavenagh, J.; Cook, G.; Cook, M.; Orti, G.; Morris, C.; Sherratt, D.; Flanagan, L.; Gregory, W.; Cavet, J. Myeloma UK Early Phase Clinical Trial Network. Bendamustine, thalidomide and dexamethasone combination therapy for relapsed/refractory myeloma patients: results of the MUKone randomized dose selection trial. Br. J. Haematol., 2015, 170, 336-348.
[12]
Sonneveld, P.; Asselbergs, E.; Zweegman, S.; van der Holt, B.; Kersten, M.J.; Vellenga, E.; van Marwijk-Kooy, M.; Broyl, A.; de Weerdt, O.; Lonergan, S.; Palumbo, A.; Lokhorst, H. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood, 2015, 125, 449-456.
[13]
Smith, S.M.; Grinblatt, D.; Johnson, J.L.; Niedzwiecki, D.; Rizzieri, D.; Bartlett, N.L.; Cheson, B.D. Cancer and Leukemia Group B. Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B. Br. J. Haematol., 2008, 140, 313-319.
[14]
Wu, H.; Zhao, C.; Gu, K.; Jiao, Y.; Hao, J.; Sun, G. Thalidomide plus chemotherapy exhibit enhanced efficacy in the clinical treatment of T-cell non-Hodgkin’s lymphoma: A prospective study of 46 cases. Mol. Clin. Oncol., 2014, 2, 695-700.
[15]
Damaj, G.; Lefrère, F.; Delarue, R.; Varet, B.; Furman, R.; Hermine, O. Thalidomide therapy induces response in relapsed mantle cell lymphoma. Leukemia, 2003, 17, 1914-1915.
[16]
Richardson, S.J.; Eve, H.E.; Copplestone, J.A.; Dyer, M.J.; Rule, S.A. Activity of thalidomide and lenalidomide in mantle cell lymphoma. Acta Haematol., 2010, 123, 21-29.
[17]
Awan, F.T.; Johnson, A.J.; Lapalombella, R.; Hu, W.; Lucas, M.; Fischer, B.; Byrd, J.C. Thalidomide and lenalidomide as new therapeutics for the treatment of chronic lymphocytic leukemia. Leuk. Lymphoma, 2010, 51, 27-38.
[18]
Pointon, J.C.; Eagle, G.; Bailey, J.; Evans, P.; Allsup, D.; Greenman, J. Thalidomide enhances cyclophosphamide and dexamethasone-mediated cytotoxicity towards cultured chronic lymphocytic leukaemia cells. Oncol. Rep., 2010, 24, 1315-1321.
[19]
Giannopoulos, K.; Mertens, D.; Stilgenbauer, S. Treating chronic lymphocytic leukemia with thalidomide and lenalidomide. Expert Opin. Pharmacother., 2011, 12, 2857-2864.
[20]
Luo, X.; Xu, Y.; Li, B.; Qin, T.; Zhang, P.; Zhang, H.; Fang, L.; Pan, L.; Hu, N.; Qu, S.; Zhang, Y.; Huang, G.; Gale, R.P.; Xiao, Z. Thalidomide plus prednisone with or without danazol therapy in myelofibrosis: a retrospective analysis of incidence and durability of anemia response. Blood Cancer J., 2018, 8, 9.
[21]
Millrine, D.; Kishimoto, T. A brighter side to lenalidomide: its potential use in immunological disorders. Trends Mol. Med., 2017, 23, 348-361.
[22]
Raza, A.; Meyer, P.; Dutt, D.; Zorat, F.; Lisak, L.; Nascimben, F.; du Randt, M.; Kaspar, C.; Goldberg, C.; Loew, J.; Dar, S.; Gezer, S.; Venugopal, P.; Zeldis, J. Thalidomide produces transfusion independence in long standing refractory anemias of patients with myelodysplastic syndromes. Blood, 2001, 98, 958-965.
[23]
Strupp, C.; Germing, U.; Aivado, M.; Misgeld, E.; Haas, R.; Gattermann, N. Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia, 2002, 16, 1-6.
[24]
Musto, P. Thalidomide therapy for myelodysplastic syndromes: Current status and future perspectives. Leuk. Res., 2004, 28, 325-332.
[25]
Invernizzi, R.; Travaglino, E.; De Amici, M.; Brugnatelli, S.; Ramajoli, I.; Rovati, B.; Benatti, C.; Ascari, E. Thalidomide treatment reduces apoptosis levels in bone marrow cells from patients with myelodysplastic syndromes. Leuk. Res., 2005, 29, 641-647.
[26]
Musto, P. Thalidomide therapy in adult patients with myelodysplastic syndrome: A north central cancer treatment group phase II trial. Cancer, 2007, 109, 1211-1212.
[27]
Hayashi, K.; Hattori, K.; Toi, F. Thalidomide is a highly effective treatment of MDS: A single-hospital experience in Japan. Int. J. Hematol., 2010, 91, 725-727.
[28]
Chung, S.Y.; Lin, S.F.; Chen, P.M.; Chang, M.C.; Kao, W.Y.; Chao, T.Y.; Hsiao, L.T.; Yen, C.C.; Yang, M.H.; Hwang, W.S.; Lin, T.L.; Chiou, T.J.; Chang, C.S. Thalidomide for the treatment of myelodysplastic syndrome in Taiwan: results of a phase II trial. Anticancer Res., 2012, 32, 3415-3419.
[29]
Zhao, W.H.; Zeng, Q.C.; Huang, B.T.; Li, B.S.; Chen, R.L. Decitabine plus thalidomide yields more sustained survival rates than decitabine monotherapy for risk-tailored elderly patients with myelodysplastic syndrome. Leuk. Res., 2015, 39, 424-428.
[30]
Corral, L.G.; Haslett, P.A.; Muller, G.V.; Chen, R.; Wong, L.M.; Ocampo, C.J.; Patterson, R.T.; Stirling, D.I.; Kaplan, G. Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J. Immunol., 1999, 163, 380-386.
[31]
Vallet, S.; Palumbo, A.; Raje, N.; Boccadoro, M.; Anderson, K.C. Thalidomide and lenalidomide: mechanism-based potential drug combinations. Leuk. Lymphoma, 2008, 49, 1238-1245.
[32]
Kotla, V.; Goel, S.; Nischal, S.; Heuck, C.; Vivek, K.; Das, B.; Verma, A. Mechanism of action of lenalidomide in hematological malignancies. J. Hematol. Oncol., 2009, 2, 36.
[33]
Sedlarikova, L.; Kubiczkova, L.; Sevcikova, S.; Hajek, R. Mechanism of immunomodulatory drugs in multiple myeloma. Leuk. Res., 2012, 36, 1218-1224.
[34]
Vo, M.C.; Anh-NguyenThi, T.; Lee, J.H.; Nguyen-Pham, T.N.; Lakshmi, T.J.; Jung, S.H.; Kim, J.H.; Lee, J.J. Lenalidomide enhances the function of dendritic cells generated from patients with multiple myeloma. Exp. Hematol., 2017, 46, 48-55.
[35]
Galustian, C.; Meyer, B.; Labarte, M.C.; Dredge, K.; Klaschka, D.; Henry, J.; Todryk, S.; Chen, R.; Muller, G.; Stirling, D.; Schafer, P.; Bartlett, J.B.; Dalgleish, A.G. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol. Immunother., 2009, 58, 1033-1045.
[36]
Davies, F.; Baz, R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev., 2010, 24(Suppl. 1), S13-S19.
[37]
Dredge, K.; Marriott, J.B.; Macdonald, C.D.; Man, H.W.; Chen, R.; Muller, G.W.; Stirling, D.; Dalgleish, A.G. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br. J. Cancer, 2002, 87, 1166-1172.
[38]
Dredge, K.; Horsfall, R.; Robinson, S.P.; Zhang, L.H.; Lu, L.; Tang, Y.; Shirley, M.A.; Muller, G.; Schafer, P.; Stirling, D.; Dalgleish, A.G.; Bartlett, J.B. Orally administrated lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc. Res., 2005, 69, 56-63.
[39]
Dankbar, B.; Padró, T.; Leo, R.; Feldmann, B.; Kropff, M.; Mesters, R.M.; Serve, H.; Berdel, W.E.; Kienast, J. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood, 2000, 95, 2630-2636.
[40]
Escoubet-Lozach, L.; Lin, I.L.; Jensen-Pergakes, K.; Brady, H.A.; Gandhi, A.K.; Schafer, P.H.; Muller, G.W.; Worland, P.J.; Chan, K.W.; Verhelle, D. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1-mediated epigenetic mechanism. Cancer Res., 2009, 69, 7347-7356.
[41]
Mitsiades, N.; Mitsiades, C.S.; Poulaki, V.; Chauhan, D.; Richardson, P.G.; Hideshima, T.; Munshi, N.C.; Treon, S.P.; Anderson, K.C. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: Therapeutic implications. Blood, 2002, 99, 4525-4530.
[42]
Chang, X.; Zhu, Y.; Shi, C.; Stewart, A.K. Mechanism of immunomodulatory drugs´ action in the treatment of multiple myeloma. Acta Biochim. Biophys. Sin. (Shanghai), 2014, 46, 240-253.
[43]
Wiernik, P.H.; Lossos, I.S.; Tuscano, J.M.; Justice, G.; Vose, J.M.; Cole, C.E.; Lam, W.; McBride, K.; Wride, K.; Pietronigro, D.; Takeshita, K.; Ervin-Haynes, A.; Zeldis, J.B.; Habermann, T.M. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J. Clin. Oncol., 2008, 26, 4952-4957.
[44]
Habermann, T.M.; Lossos, I.S.; Justice, G.; Vose, J.M.; Wiernik, P.H.; McBride, K.; Wride, K.; Ervin-Haynes, A.; Takeshita, K.; Pietronigro, D.; Zeldis, J.B.; Tuscano, J.M. Lenalidomide oral monotherapy produces a high response rate patients with relapsed or refractory mantle cell lymphoma. Br. J. Haematol., 2009, 145, 344-349.
[45]
Witzig, T.E.; Vose, J.M.; Zinzani, P.L.; Reeder, C.B.; Buckstein, R.; Polikoff, J.A.; Bouabdallah, R.; Haioun, C.; Tilly, H.; Guo, P.; Pietronigro, D.; Ervin-Haynes, A.L.; Czuczman, M.S. An international phase II trial of single agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann. Oncol., 2011, 22, 1622-1627.
[46]
Eve, H.E.; Carey, S.; Richardson, S.J.; Heise, C.C.; Mamidipudi, V.; Shi, T.; Radford, J.A.; Auer, R.L.; Bullard, S.H.; Rule, S.A. Single-agent lenalidomide in relapsed / refractory mantle cell lymphoma: Results from a UK phase II study suggest activity and possible gender differences. Br. J. Haematol., 2012, 159, 154-163.
[47]
Pan, B.; Lentzsch, S. The application and biology of immunomodulatory drugs (IMiDs) in cancer. Pharmacol. Ther., 2012, 136, 56-68.
[48]
Dawar, R.; Hernandez-Ilizalilutti, F. The emerging role of lenalidomide in the management of mantle cell lymphoma (MCL). Best Pract. Res. Clin. Haematol., 2012, 25, 185-190.
[49]
Goy, A.; Sinha, R.; Williams, M.E.; Kalayoglu Besisik, S.; Drach, J.; Ramchandren, R.; Zhang, L.; Cicero, S.; Fu, T.; Witzig, T.E. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: Phase II MCL-001 (EMERGE) study. J. Clin. Oncol., 2013, 31, 3688-3695.
[50]
Zinzani, P.L.; Vose, J.M.; Czuczman, M.S.; Reeder, C.B.; Haioun, C.; Polikoff, J.; Tilly, H.; Zhang, L.; Prandi, K.; Li, J.; Witzig, T.E. Long-term follow-up of lenalidomide in relapsed/refractory mantle-cell lymphoma: subset analysis of the NHL-003 study. Ann. Oncol., 2013, 24, 2892-2897.
[51]
Zhang, L.H.; Kosek, J.; Wang, M.; Heise, C.; Schafer, P.H.; Chopra, R. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br. J. Haematol., 2013, 160, 487-502.
[52]
Kritharis, A.; Coyle, M.; Sharma, J.; Evens, A.M. Lenalidomide in non-Hodgkin lymphoma: Biological perspectives and therapeutic opportunities. Blood, 2015, 125, 2471-2476.
[53]
Chen, C.I. Lenalidomide alone and in combination for chronic lymphocytic leukemia. Curr. Hematol. Malig. Rep., 2013, 8, 7-13.
[54]
Kater, A.P.; Tonino, S.H.; Egle, A.; Ramsay, A.G. How does lenalidomide target the chronic lymphocytic leukemia microenvironment? Blood, 2014, 124, 2184-2189.
[55]
Liberati, A.M.; Vitolo, U.; Palumbo, A.; Cortelezzi, A. Lenalidomide in the treatment of lymphoproliferative disorders and multiple myeloma. Adv. Hematol., 2013, 2013, 812605.
[56]
Yang, B.; Yu, R.L.; Chi, X.H.; Lu, X.C. Lenalidomide treatment for multiple myeloma: Systematic review and meta analysis of randomized controlled trials. PLoS One, 2013, 8, e64354.
[57]
Dimopoulos, M.A.; Terpos, E.; Niesvizky, R. How lenalidomide is changing the treatment of patients with multiple myeloma. Crit. Rev. Oncol. Hematol., 2013, 88(Suppl. 1), S23-S35.
[58]
Cives, M.; Simone, V.; Brunetti, O.; Longo, V.; Silvestris, F. Novel lenalidomide-based combinations for treatment of multiple myeloma. Crit. Rev. Oncol. Hematol., 2013, 85, 9-20.
[59]
Zago, M.; Oehrlein, K.; Rendl, C.; Hahn-Ast, C.; Kanz, L.; Weisel, K. Lenalidomide in relapsed and refractory multiple myeloma disease: Feasibility and benefits of long-term treatment. Ann. Hematol., 2014, 93, 1993-1999.
[60]
Popat, R.; Khan, I.; Dickson, J.; Cheesman, S.; Smith, D.; D’Sa, S.; Rabin, N.; Yong, K. An alternative dosing strategy of lenalidomide for patients with relapsed multiple myeloma. Br. J. Haematol., 2015, 168, 148-151.
[61]
Moreau, P.; Attal, M.; Facon, T. Frontline therapy of multiple myeloma. Blood, 2015, 125, 3076-3084.
[62]
Zagouri, F.; Terpos, E.; Kastritis, E.; Dimopoulos, M.A. An update on the use of lenalidomide for the treatment of multiple myeloma. Expert Opin. Pharmacother., 2015, 16, 1865-1877.
[63]
Kim, Y.; Schmidt-Wolf, I.G. Lenalidomide in multiple myeloma. Expert Rev. Anticancer Ther., 2015, 15, 491-497.
[64]
Kuroda, J.; Kobayashi, T.; Taniwaki, M. Prognostic indicators of lenalidomide for multiple myeloma: consensus and controversy. Expert Rev. Anticancer Ther., 2015, 15, 787-804.
[65]
Fink, E.C.; Ebert, B.L. The novel mechanism of lenalidomide activity. Blood, 2015, 126, 2366-2369.
[66]
Lacy, M.Q.; Hayman, S.R.; Gertz, M.A.; Dispenzieri, A.; Buadi, F.; Kumar, S.; Greipp, P.R.; Lust, J.A.; Russell, S.J.; Dingli, D.; Kyle, R.A.; Fonseca, R.; Bergsagel, P.L.; Roy, V.; Mikhael, J.R.; Stewart, A.K.; Laumann, K.; Allred, J.B.; Mandrekar, S.J.; Rajkumar, S.V. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J. Clin. Oncol., 2009, 27, 5008-5014.
[67]
Lacy, M.Q.; Hayman, S.R.; Gertz, M.A.; Short, K.D.; Dispenzieri, A.; Kumar, S.; Greipp, P.R.; Lust, J.A.; Russell, S.J.; Dingli, D.; Zeldenrust, S.; Fonseca, R.; Bergsagel, P.L.; Roy, V.; Mikhael, J.R.; Stewart, A.K.; Laumann, K.; Allred, J.B.; Mandrekar, S.J.; Rajkumar, S.V.; Buadi, F. Pomalidomide (CC4047) plus low-dose dexamethasone (Pom/dex) is active and well tolerated in lenalidomide refractory multiple myeloma (MM). Leukemia, 2010, 24, 1934-1939.
[68]
Schey, S.; Ramasamy, K. Pomalidomide therapy for myeloma. Expert Opin. Investig. Drugs, 2011, 20, 691-700.
[69]
Richardson, P.G.; Siegel, D.; Baz, R.; Kelley, S.L.; Munshi, N.C.; Laubach, J.; Sullivan, D.; Alsina, M.; Schlossman, R.; Ghobrial, I.M.; Doss, D.; Loughney, N.; McBride, L.; Bilotti, E.; Anand, P.; Nardelli, L.; Wear, S.; Larkins, G.; Chen, M.; Zaki, M.H.; Jacques, C.; Anderson, K.C. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood, 2013, 121, 1961-1967.
[70]
Leleu, X.; Attal, M.; Arnulf, B.; Moreau, P.; Traulle, C.; Marit, G.; Mathiot, C.; Petillon, M.O.; Macro, M.; Roussel, M.; Pegourie, B.; Kolb, B.; Stoppa, A.M.; Hennache, B.; Bréchignac, S.; Meuleman, N.; Thielemans, B.; Garderet, L.; Royer, B.; Hulin, C.; Benboubker, L.; Decaux, O.; Escoffre-Barbe, M.; Michallet, M.; Caillot, D.; Fermand, J.P.; Avet-Loiseau, H.; Facon, T. Intergroupe Francophone du Myélome. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide-refractory multiple myeloma: Intergroupe Francophone du Myelome 2009-02. Blood, 2013, 121, 1968-1975.
[71]
Miguel, J.S.; Weisel, K.; Moreau, P.; Lacy, M.; Song, K.; Delforge, M.; Karlin, L.; Goldschmidt, H.; Banos, A.; Oriol, A.; Alegre, A.; Chen, C.; Cavo, M.; Garderet, L.; Ivanova, V.; Martinez-Lopez, J.; Belch, A.; Palumbo, A.; Schey, S.; Sonneveld, P.; Yu, X.; Sternas, L.; Jacques, C.; Zaki, M.; Dimopoulos, M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised open-label phase 3 trial. Lancet Oncol., 2013, 14, 1055-1066.
[72]
Richardson, P.G.; Siegel, D.; Vij, R.; Hofmeister, C.C.; Baz, R.; Jagannath, S.; Chen, C.; Lonial, S.; Jakubowiak, A.; Bahlis, N.; Song, K.; Belch, A.; Raje, N.; Shustik, C.; Lentzsch, S.; Lacy, M.; Mikhael, J.; Matous, J.; Vesole, D.; Chen, M.; Zaki, M.H.; Jacques, C.; Yu, Z.; Anderson, K.C. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood, 2014, 123, 1826-1832.
[73]
Clark, S.M.; Steinbach, A.; Clemmons, A.B. Pomalidomide for the treatment of multiple myeloma. J. Adv. Pract. Oncol., 2014, 5, 51-56.
[74]
Dimopoulos, M.A.; Leleu, X.; Palumbo, A.; Moreau, P.; Delforge, M.; Cavo, M.; Ludwig, H.; Morgan, G.J.; Davies, F.E.; Sonneveld, P.; Schey, S.A.; Zweegman, S.; Hansson, M.; Weisel, K.; Mateos, M.V.; Facon, T.; Miguel, J.F. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma. Leukemia, 2014, 28, 1573-1585.
[75]
Mark, T.M.; Coleman, M.; Niesvizky, R. Preclinical and clinical results with pomalidomide in the treatment of relapsed / refractory multiple myeloma. Leuk. Res., 2014, 38, 517-524.
[76]
Leleu, X.; Karlin, L.; Macro, M.; Hulin, C.; Garderet, L.; Roussel, M.; Arnulf, B.; Pegourie, B.; Kolb, B.; Stoppa, A.M.; Brechiniac, S.; Marit, G.; Thielemans, B.; Onraed, B.; Mathiot, C.; Banos, A.; Lacotte, L.; Tiab, M.; Dib, M.; Fuzibet, J.G.; Petillon, M.O.; Rodon, P.; Wetterwald, M.; Royer, B.; Legros, L.; Benboubker, L.; Decaux, O.; Escoffre-Barbe, M.; Caillot, D.; Fermand, J.P.; Moreau, P.; Attal, M.; Avet-Loiseau, H.; Facon, T. Intergroupe Francophone du Myélome (IFM). Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results. Blood, 2015, 125, 1411-1417.
[77]
San Miguel, J.F.; Weisel, K.C.; Song, K.W.; Delforge, M.; Karlin, L.; Goldschmidt, H.; Moreau, P.; Banos, A.; Oriol, A.; Garderet, L.; Cavo, M.; Ivanova, V.; Alegre, A.; Martinez-Lopez, J.; Chen, C.; Renner, C.; Bahlis, N.J.; Yu, X.; Teasdale, T.; Sternas, L.; Jacques, C.; Zaki, M.H.; Dimopoulos, M.A. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. Haematologica, 2015, 100, 1334-1339.
[78]
Krämer, I.; Engelhardt, M.; Fichtner, S.; Neuber, B.; Medenhoff, S.; Bertsch, U.; Hillengass, J.; Raab, M.S.; Hose, D.; Ho, A.D.; Goldschmidt, H.; Hundemer, M. Lenalidomide enhances myeloma-specific T-cell responses in vivo and in vitro. OncoImmunology, 2016, 5, e1139662.
[79]
Neuber, B.; Dai, J.; Waraich, W.A.; Neuber, B.; Dai, J.; Waraich, W.A. Lenalidomide overcomes the immunosuppression of regulátory CD8+CD28- T-cells. Oncotarget, 2017, 8, 98200-98214.
[80]
Giuliani, M.; Janji, B.; Berchem, G. Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression. Oncotarget, 2017, 8, 24031-24044.
[81]
Ito, T.; Ando, H.; Suzuki, T.; Ogura, T.; Hotta, K.; Imamura, Y.; Yamaguchi, Y.; Handa, H. Identification of a primary target of thalidomide teratogenicity. Science, 2010, 327, 1345-1350.
[82]
Lopez-Girona, A.; Mendy, D.; Ito, T.; Miller, K.; Gandhi, A.K.; Kang, J.; Karasawa, S.; Carmel, G.; Jackson, P.; Abbasian, M.; Mahmoudi, A.; Cathers, B.; Rychak, E.; Gaidarova, S.; Chen, R.; Schafer, P.H.; Handa, H.; Daniel, T.O.; Evans, J.F.; Chopra, R. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia, 2012, 26, 2326-2335.
[83]
Chang, X.B.; Stewart, A.K. What is the functional role of the thalidomide binding protein cereblon? Int. J. Biochem. Mol. Biol., 2011, 2, 287-294.
[84]
Fischer, E.S.; Böhm, K.; Lydeard, J.R.; Yang, H.; Stadler, M.B.; Cavadini, S.; Nagel, J.; Serluca, F.; Acker, V.; Lingaraju, G.M.; Tichkule, R.B.; Schebesta, M.; Forrester, W.C.; Schirle, M.; Hassiepen, U.; Ottl, J.; Hild, M.; Beckwith, R.E.; Harper, J.W.; Jenkins, J.L.; Thomä, N.H. Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with thalidomide. Nature, 2014, 512, 49-53.
[85]
Chamberlain, P.P.; Lopez-Girona, A.; Miller, K.; Carmel, G.; Pagarigan, B.; Chie-Leon, B.; Rychak, E.; Corral, L.G.; Ren, Y.J.; Wang, M.; Riley, M.; Delker, S.L.; Ito, T.; Ando, H.; Mori, T.; Hirano, Y.; Handa, H.; Hakoshima, T.; Daniel, T.O.; Cathers, B.E. Stucture of the human cereblon-DDB1-lenalidomide complex reveals basis for responsiveness to thalidomide analogs. Nat. Struct. Mol. Biol., 2014, 21, 803-809.
[86]
Lupas, A.N.; Zhu, H.; Korycinski, M. The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the β-tent fold. PLOS Comput. Biol., 2015, 11, e1004023.
[87]
Hartmann, M.D.; Boichenko, I.; Coles, M.; Lupas, A.N.; Hernandez Alvarez, B. Structural dynamics of cereblon ligand binding domain.PLOS ONE, 2015, 10, e 0128342,
[88]
Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem., 1998, 67, 425-479.
[89]
Pickart, C.M. Mechanisms underlying ubiquitination. Annu. Rev. Biochem., 2001, 70, 503-533.
[90]
Glickman, M.H.; Ciechanover, A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev., 2002, 82, 373-428.
[91]
Pickart, C.M.; Cohen, R.E. Proteasomes and their kin: proteases in the machine age. Nat. Rev. Mol. Cell Biol., 2004, 5, 177-187.
[92]
Golab, J.; Bauer, T.M.; Daniel, V.; Naujokat, C. Role of the ubiquitin-proteasome pathway in the diagnosis of human diseases. Clin. Chim. Acta, 2004, 340, 27-40.
[93]
Hershko, A. Review: Nobel Lecture. The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell Death Differ., 2005, 12, 1191-1197.
[94]
Rose, I. Review: Nobel Lecture. Ubiquitin at Fox Chase. Cell Death Differ., 2005, 12, 1162-1166.
[95]
Ciechanover, A. Intracellular protein degradation from a vague idea through the lysosome and the ubiquitin-proteasome system and on to human diseases and drug targeting: Nobel Lecture, December 8, 2004. Ann. N. Y. Acad. Sci., 2007, 1116, 1-28.
[96]
Ciechanover, A. Tracing the history of the ubiquitin proteolytic system: The pioneering article. Biochem. Biophys. Res. Commun., 2009, 387, 1-10.
[97]
Orlowski, R.Z. The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ., 1999, 6, 303-313.
[98]
Wójcik, C. Regulation of apoptosis by the ubiquitin and proteasome pathway. J. Cell. Mol. Med., 2002, 6, 25-48.
[99]
Kinyamu, H.K.; Chen, J.; Archer, T.K. Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors. J. Mol. Endocrinol., 2005, 34, 281-297.
[100]
Sun, Y. E3 ubiquitin ligases as cancer targets and biomarkers. Neoplasia, 2006, 8, 645-654.
[101]
Nalepa, G.; Rolfe, M.; Wade Harper, J. Drug discovery in the ubiquitin-proteasome system. Nat. Rev. Drug Discov., 2006, 5, 596-613.
[102]
Kitagawa, K.; Kotake, Y.; Kitagawa, M. Ubiquitin-mediated control of oncogene and tumor suppressor gene products. Cancer Sci., 2009, 100, 1374-1381.
[103]
Bassermann, T.; Eichner, R.; Pagano, M. The ubiquitin proteasome system-Implications for cell cycle control and the targeted treatment of cancer. Biochim. Biophys. Acta, 2014, 1843, 150-162.
[104]
Metzger, M.B.; Pruneda, J.N.; Klevit, R.E.; Weissman, A.M. RING-type E3 ligases: Master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim. Biophys. Acta, 2014, 1843, 47-60.
[105]
Ciechanover, A.; Stanhill, A. The complexity of recognition of ubiquitinated substrates by 26 S proteasome. Biochim. Biophys. Acta, 2014, 1843, 86-96.
[106]
Krӧnke, J.; Udeshi, N.D.; Narla, A.; Grauman, P.; Hurst, S.N.; McConkey, M.; Svinkina, T.; Heckl, D.; Comer, E.; Li, X.; Ciarlo, C.; Hartman, E.; Munshi, N.; Schenone, M.; Schreiber, S.L.; Carr, S.A.; Ebert, B.L. Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science, 2014, 343, 301-305.
[107]
Lu, G.; Middleton, R.E.; Sun, H.; Naniong, M.; Ott, C.J.; Mitsiades, C.S.; Wong, K.K.; Bradner, J.E.; Kaelin, W.G., Jr The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science, 2014, 343, 305-309.
[108]
Gandhi, A.K.; Kang, J.; Havens, C.G.; Conklin, T.; Ning, Y.; Wu, L.; Ito, T.; Ando, H.; Waldman, M.F.; Thakurta, A.; Klippel, A.; Handa, H.; Daniel, T.O.; Schafer, P.H.; Chopra, R. Immunomodulatory agents lenalidomide and pomalidomide co-stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN. Br. J. Haematol., 2014, 164, 811-821.
[109]
Stewart, A.K. How thalidomide works against cancer. Science, 2014, 343, 256-257.
[110]
Zhu, Y.X.; Braggio, E.; Shi, C.X.; Kortuem, K.M.; Bruins, L.A.; Schmidt, J.E.; Chang, X.B.; Langlais, P.; Luo, M.; Jedlowski, P.; LaPlant, B.; Laumann, K.; Fonseca, R.; Bergsagel, P.L.; Mikhael, J.; Lacy, M.; Champion, M.D.; Stewart, A.K. Identification of cereblon-binding proteins and relationship with response and survival after IMiDs in multiple myeloma. Blood, 2014, 124, 536-545.
[111]
Semeraro, M.; Galluzzi, L. Novel insights into the mechanism of action of lenalidomide.Oncoimmunology, 2014, 3, e 28386,
[112]
Keevan, J.; Figg, W.D. New mechanism of lenalidomide activity. Cancer Biol. Ther., 2014, 15, 968-969.
[113]
Shaffer, A.L.; Tolga Emre, N.C.; Lamy, L.; Ngo, V.N.; Wright, G.; Xiao, W.; Powell, J.; Dave, S.; Yu, X.; Zhao, H.; Zeng, Y.; Chen, B.; Epstein, J.; Staudt, L.M. IRF4 addiction in multiple myeloma. Nature, 2008, 454, 226-231.
[114]
Shaffer, A.L.; Tolga Emre, N.C.; Romesser, P.B.; Staudt, L.M. IRF4: Immunity. Malignancy! Therapy? Clin. Cancer Res., 2009, 15, 2954-2961.
[115]
Lopez-Girona, A.; Heintel, D.; Zhang, L.H.; Mendy, D.; Gaidarova, S.; Brady, H.; Bartlett, J.B.; Schafer, P.H.; Schreder, M.; Bolomsky, A.; Hilgarth, B.; Zojer, N.; Gisslinger, H.; Ludwig, H.; Daniel, T.; Jäger, U.; Chopra, R. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br. J. Haematol., 2011, 154, 325-336.
[116]
Krönke, J.; Fink, E.C.; Hollenbach, P.W.; MacBeth, K.J.; Hurst, S.N.; Udeshi, N.D.; Chamberlain, P.P.; Mani, D.R.; Man, H.W.; Gandhi, A.K.; Svinkina, T.; Schneider, R.K.; McConkey, M.; Järås, M.; Griffiths, E.; Wetzler, M.; Bullinger, L.; Cathers, B.E.; Carr, S.A.; Chopra, R.; Ebert, B.L. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature, 2015, 523, 183-188.
[117]
Bjorklund, C.C.; Lu, L.; Kang, J.; Hagner, P.R.; Havens, C.G.; Amatangelo, M.; Wang, M.; Ren, Y.; Couto, S.; Breider, M.; Ning, Y.; Gandhi, A.K.; Daniel, T.O.; Chopra, R.; Klippel, A.; Thakurta, A.G. Rate of CRL4 (CRBN) substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in MM cells by regulation of c-Myc and IRF4. Blood Cancer J., 2015, 5, e 354.
[118]
Petroski, M.D.; Deshales, R.J. Function and regulation of cullin-RING ubiquitin ligases. Nat. Rev. Mol. Cell Biol., 2005, 6, 9-20.
[119]
Jin, J.; Arias, E.E.; Chen, J.; Wade Harper, J.; Walter, J.C. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol. Cell, 2006, 23, 709-721.
[120]
Li, T.; Chen, X.; Garbutt, K.C.; Zhou, P.; Zheng, N. Structure of DDB1 in complex with a ParamyxovirusV protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell, 2006, 124, 105-117.
[121]
Angers, S.; Li, T.; Yi, X.; MacCoss, M.J.; Moon, R.T.; Zheng, N. Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase machinery. Nature, 2006, 443, 590-593.
[122]
Lee, J.; Zhou, P. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol. Cell, 2007, 26, 775-780.
[123]
Catic, A. Culling for survival. Blood, 2008, 112, 211-212.
[124]
Waning, D.L.; Li, B.; Jia, N.; Naaldijk, Y.; Goebel, W.S. HogenEsch, H.; Chun, K.T. Cul 4A is required for hematopoietic cell viability and its deficiency leads to apoptosis. Blood, 2008, 112, 320-329.
[125]
Jackson, S.; Xiong, Y. CRL4s: The CUL4-RING E3 ubiquitin ligases. Trends Biochem. Sci., 2009, 34, 562-570.
[126]
Sugasawa, K. The CUL4 enigma: Culling DNA repair factors. Mol. Cell, 2009, 34, 403-404.
[127]
Lee, J.; Zhou, P. Pathogenic role of the CRL4 ubiquitin ligase in human disease. Front. Oncol., 2012, 2, 1-7.
[128]
Zhao, Y.; Sun, Y. Cullin-RING ligases as attractive anti-cancer targets. Curr. Pharm. Des., 2013, 19, 3215-3225.
[129]
Pan, Z.Q.; Kentsis, A.; Dias, D.C.; Yamoah, K.; Wu, K. Nedd8 on cullin: building an express way to protein destruction. Oncogene, 2004, 23, 1985-1997.
[130]
Merlet, J.; Burger, J.; Gomes, J.E.; Pintard, L. Regulation of cullin-RING E3 ubiquitin-ligases by neddylation and dimerization. Cell. Mol. Life Sci., 2009, 66, 1924-1938.
[131]
Lydeard, J.R.; Schulman, B.A.; Harper, J.W. Building and remodelling cullin-ring E3 ubiquitin ligases. EMBO Rep., 2013, 14, 1050-1061.
[132]
Kortűm, K.M.; Zhu, Y.X.; Shi, C.X.; Jedlowski, P.; Stewart, A.K. Cereblon binding molecules in multiple myeloma. Blood Rev., 2015, 29, 329-334.
[133]
Xu, Q.; Hou, Y.X.; Langlais, P.; Erickson, P.; Zhu, J.; Shi, C.X.; Luo, M.; Zhu, Y.; Xu, Y.; Mandarino, L.J.; Stewart, K.; Chang, X.B. Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. BMC Cancer, 2016, 16, 297.
[134]
He, Y.J.; McCall, C.M.; Hu, J.; Zeng, Y.; Xiong, Y. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev., 2006, 20, 2949-2954.
[135]
Iovine, B.; Iannella, M.L.; Bevilacqua, M.A. Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions. Int. J. Biochem. Cell Biol., 2011, 43, 1664-1667.
[136]
Komatsu, M.; Kageyama, S.; Ichimura, Y. p62/SQSTM1/A170: physiology and pathology. Pharmacol. Res., 2012, 66, 457-462.
[137]
Fuchs, O.; Bokorova, R.; Vostry, M.; Kostečka, A.; Polak, J. Cereblon and its role in the treatment of multiple myeloma by lenalidomide and pomalidomide. Int. J. Hematol. Dis, 2014, 1, 13-20.
[138]
Zhu, Y.X.; Braggio, E.; Shi, C.X.; Bruins, L.A.; Schmidt, J.E.; Van Wier, S.; Chang, X.B.; Bjorklund, C.C.; Fonseca, R.; Bergsagel, P.L.; Orlowski, R.Z.; Stewart, A.K. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood, 2011, 118, 4771-4779.
[139]
Broyl, A.; Kuiper, R.; van Duin, M.; van der Holt, B.; el Jarari, L.; Bertsch, U.; Zweegman, S.; Buijs, A.; Hose, D.; Lokhorst, H.M.; Goldschmidt, H.; Sonneveld, P. Dutch-Belgian HOVON group;German GMMG Group. High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance. Blood, 2013, 121, 624-627.
[140]
Heintel, D.; Rocci, A.; Ludwig, H.; Bolomsky, A.; Caltagirone, S.; Schreder, M.; Pfeifer, S.; Gisslinger, H.; Zojer, N.; Jäger, U.; Palumbo, A. High expression of cereblon (CRBN) is associated with improved clinical response in patients with multiple myeloma treated with lenalidomide and dexamethasone. Br. J. Haematol., 2013, 161, 695-700.
[141]
Lodé, L.; Amiot, M.; Maiga, S.; Touzeau, C.; Menard, A.; Magrangeas, F.; Minvielle, S.; Pellat-Deceunynck, C.; Bene, M.C.; Moreau, P. Cereblon expression in multiple myeloma: not ready for prime time. Br. J. Haematol., 2013, 163, 282-284.
[142]
Gandhi, A.K.; Mendy, D.; Waldman, M.; Chen, G.; Rychak, E.; Miller, K.; Gaidarova, S.; Ren, Y.; Wang, M.; Breider, M.; Carmel, G.; Mahmoudi, A.; Jackson, P.; Abbasian, M.; Cathers, B.E.; Schafer, P.H.; Daniel, T.O.; Lopez-Girona, A.; Thakurta, A.; Chopra, R. Measuring cereblon as a biomarker of response or resistance to lenalidomide and pomalidomide requires use of standardized reagents and understanding of gene complexity. Br. J. Haematol., 2014, 164, 233-244.
[143]
Pearse, R.N. IMiDs: Not for the CRBN weak. Leuk. Res., 2014, 38, 21-22.
[144]
Schuster, S.R.; Kortuem, K.M.; Zhu, Y.X.; Braggio, E.; Shi, C.X.; Bruins, L.A.; Schmidt, J.E.; Ahmann, G.; Kumar, S.; Rajkumar, S.V.; Mikhael, J.; Laplant, B.; Champion, M.D.; Laumann, K.; Barlogie, B.; Fonseca, R.; Bergsagel, P.L.; Lacy, M.; Stewart, A.K. The clinical significance of cereblon expression in multiple myeloma. Leuk. Res., 2014, 38, 23-28.
[145]
Zhu, Y.X.; Kortuem, K.M.; Stewart, A.K. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk. Lymphoma, 2013, 54, 683-687.
[146]
Jonasova, A.; Bokorova, R.; Polak, J.; Vostry, M.; Kostecka, A.; Hajkova, H.; Neuwirtova, R.; Siskova, M.; Sponerova, D.; Cermak, J.; Mikulenkova, D.; Cervinek, L.; Brezinova, J.; Michalova, K.; Fuchs, O. High level of full-length cereblon mRNA in lower risk myelodysplastic syndrome with isolated 5q deletion is implicated in the efficacy of lenalidomide. Eur. J. Haematol., 2015, 95, 27-34.
[147]
Fuchs, O.; Polak, J.; Bokorova, R.; Kostecka, A.; Vostry, M.; Neuwirtova, R.; Siskova, M.; Stopka, T.; Lauermannova, M.; Soukupova-Maaloufova, J.; Salek, C.; Mikulenkova, D.; Cermak, J.; Brezinova, J.; Zemanova, Z.; Michalova, K.; Jonasova, A. High level of full-length cereblon messenger RNA and protein is important for lenalidomide efficacy in lower risk MDS patients.Abstract 227 from the 14th International Symposium on Myelodysplastic Syndromes. Leuk. Res., 2017, 55(Suppl 1), S 132.
[148]
Lee, K.J.; Lee, K.M.; Jo, S.; Kang, K.W.; Park, C.S. Induction of cereblon by NF-E2-related factor 2 in neuroblastoma cells exposed to hypoxia-reoxygenation. Biochem. Biophys. Res. Commun., 2010, 399, 711-715.
[149]
Lionetti, M.; Agnelli, L.; Lombardi, L.; Tassone, P.; Neri, A. MicroRNAs in the pathobiology of multiple myeloma. Curr. Cancer Drug Targets, 2012, 12, 823-837.
[150]
Wu, P.; Agnelli, L.; Walker, B.A.; Todoerti, K.; Lionetti, M.; Johnson, D.C.; Kaiser, M.; Mirabella, F.; Wardell, C.; Gregory, W.M.; Davies, F.E.; Brewer, D.; Neri, A.; Morgan, G.J. Improved risk stratification in myeloma using a microRNA-based classifier. Br. J. Haematol., 2013, 162, 348-359.
[151]
Bi, C.; Chng, W.J. MicroRNA: important player in the pathobiology of multiple myeloma. Biomed. Res. Inst, 2014, 2014, 521586.
[152]
Greenberg, A.J.; Walters, D.K.; Kumar, S.K.; Rajkumar, S.V.; Jelinek, D.F. Responsiveness of cytogenetically discrete human myeloma cell lines to lenalidomide: lack of correlation with cereblon and interferon regulatory factor 4 expression levels. Eur. J. Haematol., 2013, 91, 504-513.
[153]
Huang, S.Y.; Lin, C.W.; Lin, H.H.; Yao, M.; Tang, J.L.; Wu, S.J.; Chen, Y.C.; Lu, H.Y.; Hou, H.A.; Chen, C.Y.; Chou, W.C.; Tsay, W.; Chou, S.J.; Tien, H.F. Expression of cereblon protein assessed by immunohistochemical staining in myeloma cells is associated with superior response of thalidomide- and lenalidomide-based treatment, but not bortezomib-based treatment, in patients with multiple myeloma. Ann. Hematol., 2014, 93, 1371-1380.
[154]
Chang, X.; Xu, Q.; Hou, Y.; Li, C.; Xu, Y.; Stewart, A.K. Mouse monoclonal antibodies generated from full length human cereblon: Detection of cereblon protein in patients with multiple myeloma. Int. J. Mol. Sci., 2017, 18, E1999.
[155]
Eichner, R.; Heider, M.; Fernández-Sáiz, V.; van Bebber, F.; Garz, A.K.; Lemeer, S.; Rudelius, M.; Targosz, B.S.; Jacobs, L.; Knorn, A.M.; Slawska, J.; Platzbecker, U.; Germing, U.; Langer, C.; Knop, S.; Einsele, H.; Peschel, C.; Haass, C.; Keller, U.; Schmid, B.; Götze, K.S.; Kuster, B.; Bassermann, F. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity. Nat. Med., 2016, 22, 735-743.
[156]
Krönke, J.; Kuchenbauer, F.; Kull, M.; Teleanu, V.; Bullinger, L.; Bunjes, D.; Greiner, A.; Kolmus, S.; Köpff, S.; Schreder, M.; Mügge, L.O.; Straka, C.; Engelhardt, M.; Döhner, H.; Einsele, H.; Bassermann, F.; Bargou, R.; Knop, S.; Langer, C. IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM). Leukemia, 2017, 31, 1363-1367.
[157]
Krönke, J.; Knop, S.; Langer, C. Prognostic impact of Ikaros expression in lenalidomide-treated multiple myeloma. Oncotarget, 2017, 8, 106163-106164.
[158]
Catley, L.; Weisberg, E.; Tai, Y.T.; Atadja, P.; Remiszewski, S.; Hideshima, T.; Mitsiades, N.; Shringarpure, R.; LeBlanc, R.; Chauhan, D.; Munshi, N.C.; Schlossman, R.; Richardson, P.; Griffin, J.; Anderson, K.C. NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood, 2003, 102, 2615-2622.
[159]
Mitsiades, C.S.; Mitsiades, N.S.; McMullan, C.J.; Poulaki, V.; Shringarpure, R.; Hideshima, T.; Akiyama, M.; Chauhan, D.; Munshi, N.; Gu, X.; Bailey, C.; Joseph, M.; Libermann, T.A.; Richon, V.M.; Marks, P.A.; Anderson, K.C. Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications. Proc. Natl. Acad. Sci. USA, 2004, 101, 540-545.
[160]
Catley, L.; Weisberg, M.E.; Kiziltepe, T.; Tai, Y.T.; Hideshima, T.; Neri, P.; Tassone, P.; Atadja, P.; Chauhan, D.; Munshi, N.C.; Anderson, K.C. Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood, 2006, 108, 3441-3449.
[161]
Richardson, P.G.; Harvey, R.D.; Laubach, J.P.; Moreau, P.; Lonial, S.; San-Miguel, J.F. Panobinostat for the treatment of relapsed or relapsed/refractory multiple myeloma: Pharmacology and clinical outcomes. Expert Rev. Clin. Pharmacol., 2016, 91, 35-48.
[162]
Sivaraj, D.; Green, M.M.; Gasparetto, C. Panobinostat for the management of multiple myeloma. Future Oncol., 2017, 13, 477-488.
[163]
Laubach, J.P.; San-Miguel, J.F.; Hungria, V.; Hou, J.; Moreau, P.; Lonial, S.; Lee, J.H.; Einsele, H.; Alsina, M.; Richardson, P.G. Deacetylase inhibitors: an advance in myeloma therapy? Expert Rev. Hematol., 2017, 10, 229-237.
[164]
Hideshima, T.; Cottini, F.; Ohguchi, H.; Jakubikova, J.; Gorgun, G.; Mimura, N.; Tai, Y.T.; Munshi, N.C.; Richardson, P.G.; Anderson, C.K. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma. Blood Cancer J., 2015, 5, e312.
[165]
Li, S.; Pal, R.; Monaghan, S.A.; Schafer, P.; Ouyang, H.; Mapara, M.; Galson, D.L.; Lentzsch, S. IMiD immunomodulatory compounds block C/EBPβ translation through eIF4E down-regulation resulting in inhibition of MM. Blood, 2011, 117, 5157-5165.
[166]
Chesi, M.; Robbiani, D.F.; Sebag, M.; Chng, W.J.; Affer, M.; Tiedemann, R.; Valdez, R.; Palmer, S.E.; Haas, S.S.; Stewart, A.K.; Fonseca, R.; Kremer, R.; Cattoretti, G.; Bergsagel, P.L. AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies. Cancer Cell, 2008, 13, 167-180.
[167]
Chesi, M.; Matthews, G.M.; Garbitt, V.M.; Palmer, S.E.; Shortt, J.; Lefebure, M.; Stewart, A.K.; Johnstone, R.W.; Bergsagel, P.L. Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy. Blood, 2012, 120, 376-385.
[168]
Affer, M.; Chesi, M.; Chen, W.D.; Keats, J.J.; Demchenko, Y.N.; Roschke, A.V.; Van Wier, S.; Fonseca, R.; Bergsagel, P.L.; Kuehl, W.M. Promiscuous MYC locus rearrangements hijack enhancers but mostly super-enhancers to dysregulate MYC expression in multiple myeloma. Leukemia, 2014, 28, 1725-1735.
[169]
Walker, B.A.; Wardell, C.P.; Brioli, A.; Boyle, E.; Kaiser, M.F.; Begum, D.B.; Dahir, N.B.; Johnson, D.C.; Ross, F.M.; Davies, F.E.; Morgan, G.J. Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients. Blood Cancer J., 2014, 4, e191.
[170]
Gopalakrishnan, R.; Matta, H.; Tolani, B.; Triche, T., Jr; Chaudhary, P.M. Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors. Oncogene, 2016, 35, 1797-1810.
[171]
Ramsay, A.G.; Johnson, A.J.; Lee, A.M.; Gorgün, G.; Le Dieu, R.; Blum, W.; Byrd, J.C.; Gribben, J.G. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J. Clin. Invest., 2008, 118, 2427-2437.
[172]
Idler, I.; Giannopoulos, K.; Zenz, T.; Bhattacharya, N.; Nothing, M.; Döhner, H.; Stilgenbauer, S.; Mertens, D. Lenalidomide treatment of chronic lymphocytic leukaemia patients reduces regulatory T cells and induces Th17 T helper cells. Br. J. Haematol., 2010, 148, 940-950.
[173]
Skórka, K.; Bhattacharya, N.; Wlasiuk, P.; Kowal, M.; Mertens, D.; Dmoszyńska, A.; Giannopoulos, K. Thalidomide regulation of NF-κB proteins limits Tregs activity in chronic lymphocytic leukemia. Adv. Clin. Exp. Med., 2014, 23, 25-32.
[174]
Lee, B.N.; Gao, H.; Cohen, E.N.; Badoux, X.; Wierda, W.G.; Estrov, Z.; Faderl, S.H.; Keating, M.J.; Ferrajoli, A.; Reuben, J.M. Treatment with lenalidomide modulates T-cell immunophenotype and cytokine poduction in patients with chronic lymphocytic leukemia. Cancer, 2011, 117, 3999-4008.
[175]
Kasyapa, C.S.; Sher, T.; Chanan-Khan, A.A. Multiple myeloma and immunomodulation: Regulating the regulatory cells. Leuk. Lymphoma, 2012, 53, 1253-1254.
[176]
Chanan-Khan, A.; Miller, K.C.; Musial, L.; Lawrence, D.; Padmanabhan, S.; Takeshita, K.; Porter, C.W.; Goodrich, D.W.; Bernstein, Z.P.; Wallace, P.; Spaner, D.; Mohr, A.; Byrne, C.; Hernandez-Ilizaliturri, F.; Chrystal, C.; Starostik, P.; Czuczman, M.S. Clinical efficiacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: Results of a phase II study. J. Clin. Oncol., 2006, 24, 5343-5349.
[177]
Ferrajoli, A.; Lee, B.N.; Schlette, E.J.; O’Brien, S.M.; Gao, H.; Wen, S.; Wierda, W.G.; Estrov, Z.; Faderl, S.; Cohen, E.N.; Li, C.; Reuben, J.M.; Keating, M.J. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood, 2008, 111, 5291-5297.
[178]
Wendtner, C.M.; Hillmen, P.; Mahadevan, D.; Bühler, A.; Uharek, L.; Coutré, S.; Frankfurt, O.; Bloor, A.; Bosch, F.; Furman, R.R.; Kimby, E.; Gribben, J.G.; Gobbi, M.; Dreisbach, L.; Hurd, D.D.; Sekeres, M.A.; Ferrajoli, A.; Shah, S.; Zhang, J.; Moutouh-de Parseval, L.; Hallek, M.; Heerema, N.A.; Stilgenbauer, S.; Chanan-Khan, A.A. Final results of a multicenter phase I study of lenalidomide in patients with relapsed or refractory chronic lymhocytic leukemia. Leuk. Lymphoma, 2012, 53, 417-423.
[179]
Wendtner, C.; Hallek, M.; Fraser, G.; Michallet, A.S.; Hillmen, P.; Dürig, J.; Kalaycio, M.; Gribben, J.G.; Stilgenbauer, S.; Buhler, A.; Kipps, T.J.; Purse, B.; Zhang, J.; De Bedout, S.; Mei, J.; Chanan-Khan, A. Safety and efficacy of different lenalidomide starting doses in patients with relapsed or refractory chronic lymphocytic leukemia: results of an international multicenter double-blinded randomized phase II trial. Leuk. Lymphoma, 2016, 57, 1291-1299.
[180]
Batoo, S.A.; Hernandez-Ilizaliturri, F. The emerging role of lenalidomide in the management of lymphoid malignancies. Ther. Adv. Hematol., 2011, 2, 45-53.
[181]
Blumel, S.; Broadway-Duren, J. Approaches to managing safety with lenalidomide in hematologic malignancies. Adv. Practitioner, 2014, 5, 269-279.
[182]
Cortelezzi, A.; Sciumé, M.; Reda, G. Lenalidomide in the treatment of chronic lymphocytic leukemia. Adv. Hematol., 2012, Article ID 393864.
[183]
James, D.F.; Werner, L.; Brown, J.R.; Wierda, W.G.; Barrientos, J.C.; Castro, J.E.; Greaves, A.; Johnson, A.J.; Rassenti, L.Z.; Rai, K.R.; Neuberg, D.; Kipps, T.J. Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicentre clinical-translational study from the chronic lymphocytic leukemia research consortium. J. Clin. Oncol., 2014, 32, 2067-2073.
[184]
Mato, A.R.; Foon, K.A.; Feldman, T.; Schuster, S.J.; Svoboda, J.; Chow, K.F.; Valentinetti, M.; Mrkulic, M.; Azzollini, K.; Gadaleta, G.; Bhattacharyya, P.K.; Zenreich, J.; Pascual, L.N.; Yannotti, K.; Kdiry, S.; Howlett, C.; Strelec, L.; Porter, D.; Bejot, C.; Goy, A. Reduced-dose fludarabine, cyclophosphamide, and rituximab (FCR-Lite) plus lenalidomide, followed by lenalidomide consolidation/maintenance, in previously untreated chronic lymphocytic leukemia. Am. J. Hematol., 2015, 90, 487-492.
[185]
Fecteau, J.F.; Corral, L.G.; Ghia, E.M.; Gaidarova, S.; Futalan, D.; Bharati, I.S.; Cathers, B.; Schwaederlé, M.; Cui, B.; Lopez-Girona, A.; Messmer, D.; Kipps, T.J. Lenalidomide inhibits the proliferation of CLL cells via a cereblon/p21(WAF1, CIP1)-dependent mechanism independent of functional p53. Blood, 2014, 124, 1637-1644.
[186]
Jamroziak, K.; Szemraj, J.; Robak, T.; Tukiendorf, A.; Giannopoulos, K. Cereblon expression predicts clinical response in chronic lymphocytic leukemia treated with a thalidomide/ fludarabine regimen. Leuk. Lymphoma, 2015, 56, 808-810.
[187]
Schulz, A.; Durr, C.; Zenz, T.; Döhner, H.; Stilgenbauer, S.; Lichter, P.; Seiffert, M. Lenalidomide reduces survival of chronic lymphocytic leukemia cells in primary cocultures by altering the myeloid microenvironment. Blood, 2013, 121, 2503-2511.
[188]
Fiorcari, S.; Martinelli, S.; Bulgarelli, J.; Audrito, V.; Zucchini, P.; Colaci, E.; Potenza, L.; Narni, F.; Luppi, M.; Deaglio, S.; Marasca, R.; Maffei, R. Lenalidomide interferes with tumor-promoting properties of nurse-like cells in chronic lymphocytic leukemia. Haematologica, 2015, 100, 253-262.
[189]
Shaim, H.; Estrov, Z.; Harris, F.; Hernandez Sanabria, M.; Liu, Z.; Ruvolo, P.; Thompson, P.A.; Ferrajoli, A.; Daher, M.; Burger, J.; Muftuoglu, M.; Imahashi, N.; Li, L.; Liu, E.; Alsuliman, A.S.; Basar, R.; Nassif Kerbauy, L.; Sobieski, C.; Gokdemir, E.; Kondo, K.; Wierda, W.; Keating, M.; Shpall, E.J.; Rezvani, K. The CXCR4-STAT3-IL-10 pathway controls the immunoregulatory function of chronic lymphocytic leukemia and is modulated by lenalidomide. Front. Immunol., 2018, 8, 1773.
[190]
Maffei, R.; Fiorcari, S.; Martinelli, S.; Benatti, S.; Bulgarelli, J.; Rizzotto, L.; Debbia, G.; Santachiara, R.; Rigolin, G.M.; Forconi, F.; Rossi, D.; Laurenti, L.; Palumbo, G.A.; Vallisa, D.; Cuneo, A.; Gaidano, G.; Luppi, M.; Marasca, R. Increased SHISA3 expression characterizes chronic lymphocytic leukemia patients sensitive to lenalidomide. Leuk. Lymphoma, 2018, 59, 423-433.
[191]
Takahashi, K.; Hu, B.; Wang, F.; Yan, Y.; Kim, E.; Vitale, C.; Patel, K.P.; Strati, P.; Gumbs, C.; Little, L.; Tippen, S.; Song, X.; Zhang, J.; Jain, N.; Thompson, P.; Garcia-Manero, G.; Kantarjian, H.; Estrov, Z.; Do, K.A.; Keating, M.; Burger, J.A.; Ferrajoli, A.; Futreal, P.A.; Wierda, W.G. Clinical implications of cancer gene mutations in patients with chronic lymphocytic leukemia treated with lenalidomide. Blood, 2018, 131, 1820-1832.
[192]
González-Rodríguez, A.P.; Payer, A.R.; Acebes-Huerta, A.; Huergo-Zapico, L.; Villa-Alvarez, M.; Gonzalez-García, E.; Gonzalez, S. Lenalidomide and chronic lymphocytic leukemia. BioMed Res. Int., 2013, 2013, 932010.
[193]
Maffei, R.; Colaci, E.; Fiorcari, S.; Martinelli, S.; Potenza, L.; Luppi, M.; Marasca, R. Lenalidomide in chronic lymphocytic leukemia: the present and future in the era of tyrosine kinase inhibitors. Crit. Rev. Oncol. Hematol., 2016, 97, 291-302.
[194]
Itchaki, G.; Brown, J.R. Lenalidomide in the treatment of chronic lymphocytic leukemia. Expert Opin. Investig. Drugs, 2017, 26, 633-650.
[195]
Siegel, R.; Ma, J.; Zou, Z.; Jemal, A. Cancer statistics, 2014. CA Cancer J. Clin., 2014, 64, 9-29.
[196]
Verhelle, D.; Corral, L.G.; Wong, K.; Mueller, J.H.; Moutouh-de Parseval, L.; Jensen-Pergakes, K.; Schafer, P.H.; Chen, R.; Glezer, E.; Ferguson, G.D.; Lopez-Girona, A.; Muller, G.W.; Brady, H.A.; Chan, K.W. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res., 2007, 67, 746-755.
[197]
Witzig, T.E.; Wiernik, P.H.; Moore, T.; Reeder, C.; Cole, C.; Justice, G.; Kaplan, H.; Voralia, M.; Pietronigro, D.; Takeshita, K.; Ervin-Haynes, A.; Zeldis, J.B.; Vose, J.M. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s lymphoma. J. Clin. Oncol., 2009, 27, 5404-5409.
[198]
Wiernik, P.H.; Lossos, I.S.; Tuscano, J.M.; Justice, G.; Vose, J.M.; Cole, C.E.; Lam, W.; McBride, K.; Wride, K.; Pietronigro, D.; Takeshita, K.; Ervin-Haynes, A.; Zeldis, J.B.; Habermann, T.M. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J. Clin. Oncol., 2008, 26, 4952-4957.
[199]
Witzig, T.E.; Nowakowski, G.S.; Habermann, T.M.; Goy, A.; Hernandez-Ilizaliturri, F.J.; Chiappella, A.; Vitolo, U.; Fowler, N.; Czuczman, M.S. A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Ann. Oncol., 2015, 26, 1667-1677.
[200]
Wang, M.; Fayad, L.; Wagner-Bartak, N.; Zhang, L.; Hagemeister, F.; Neelapu, S.S.; Samaniego, F.; McLaughlin, P.; Fanale, M.; Younes, A.; Cabanillas, F.; Fowler, N.; Newberry, K.J.; Sun, L.; Young, K.H.; Champlin, R.; Kwak, L.; Feng, L.; Badillo, M.; Bejarano, M.; Hartig, K.; Chen, W.; Chen, Y.; Byrne, C.; Bell, N.; Zeldis, J.; Romaguera, J. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase I/II clinical trial. Lancet Oncol., 2012, 13, 716-723.
[201]
Ahmadi, T.; Chong, E.A.; Gordon, A.; Aqui, N.A.; Nasta, S.D.; Svoboda, J.; Mato, A.R.; Schuster, S.J. Combined lenalidomide, low-dose dexamethasone, and rituximab achieves durable responses in rituximab-resistant indolent and mantle cell lymphomas. Cancer, 2014, 120, 222-228.
[202]
Chong, E.A.; Ahmadi, T.; Aqui, N.A.; Svoboda, J.; Nasta, S.D.; Mato, A.R.; Walsh, K.M.; Schuster, S.J. Combination of lenalidomide and rituximab overcomes rituximab resistance in patients with indolent B-cell and mantle cell lymphomas. Clin. Cancer Res., 2015, 21, 1835-1842.
[203]
Yang, Y.; Shaffer, A.L., III; Emre, N.C.; Ceribelli, M.; Zhang, M.; Wright, G.; Xiao, W.; Powell, J.; Platig, J.; Kohlhammer, H.; Young, R.M.; Zhao, H.; Yang, Y.; Xu, W.; Buggy, J.J.; Balasubramanian, S.; Mathews, L.A.; Shinn, P.; Guha, R.; Ferrer, M.; Thomas, C.; Waldmann, T.A.; Staudt, L.M. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell, 2012, 21, 723-737.
[204]
Avivi, I.; Goy, A. Refining the mantle cell lymphoma paradigm: Impact of novel therapies on current practice. Clin. Cancer Res., 2015, 21, 3853-3861.
[205]
Gribben, J.G.; Fowler, N.; Morschhauser, F. Mechanisms of action of lenalidomide in B-cell non-Hodgkin lymphoma. J. Clin. Oncol., 2015, 33, 2803-2811.
[206]
Otáhal, P.; Průková, D.; Král, V.; Fabry, M.; Vočková, P.; Latečková, L.; Trněný, M.; Klener, P. Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells. OncoImmunology, 2015, 5, e1115940.
[207]
Arora, M.; Gowda, S.; Tuscano, J. A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma. Ther. Adv. Hematol., 2016, 7, 209-221.
[208]
Garciaz, S.; Coso, D.; Schiano de Colella, J.M.; Bouabdallah, R. Lenalidomide for the treatment of B-cell lymphoma. Expert Opin. Investig. Drugs, 2016, 25, 1103-1116.
[209]
Martin, P.; Jung, S.H.; Pitcher, B.; Bartlett, N.L.; Blum, K.A.; Shea, T.; Hsi, E.D.; Ruan, J.; Smith, S.E.; Leonard, J.P.; Cheson, B.D. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin’s lymphoma (NHL): CALGB 50803 (Aliance). Ann. Oncol., 2017, 28, 2806-2812.
[210]
Witzig, T.E.; Luigi Zinzani, P.; Habermann, T.M.; Tuscano, J.M.; Drach, J.; Ramchandren, R.; Kalayoglu Besisik, S.; Takeshita, K.; Casadebaig Bravo, M.L.; Zhang, L.; Fu, T.; Goy, A. Long-term analysis of phase II studies of single-agent lenalidomide in relapsed/refractory mantle cell lymphoma. Am. J. Hematol., 2017, 92, E575-E583.
[211]
Henry, J.Y.; Labarthe, M.C.; Meyer, B.; Dasgupta, P.; Dalgleish, A.G.; Galustian, C. Enhanced cross-priming of naive CD8+ T cells by dendritic cells treated by the IMiDs® immunomodulatory compounds lenalidomide and pomalidomide. Immunology, 2013, 139, 377-385.
[212]
Schafer, P.H.; Gandhi, A.K.; Loveland, M.A.; Chen, R.S.; Man, H.W.; Schnetkamp, P.P.; Wolbring, G.; Govinda, S.; Corral, L.G.; Payvandi, F.; Muller, G.W.; Stirling, D.I. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J. Pharmacol. Exp. Ther., 2003, 305, 1222-1232.
[213]
Martiniani, R.; Di Loreto, V.; Di Sano, C.; Lombardo, A.; Liberati, A.M. Biological activity of lenalidomide and its underlying therapeutic effects in multiple myeloma. Adv. Hematol., 2012, 2012, 842945.
[214]
Mitsiades, C.S.; Mitsiades, N.S.; Richardson, P.G.; Munshi, N.C.; Anderson, K.C. Multiple myeloma: a prototypic disease model for the characterization and therapeutic targeting of interactions between tumor cells and their local microenvironment. J. Cell. Biochem., 2007, 101, 950-968.
[215]
Ghosh, N.; Grunwald, M.R.; Fasan, O.; Bhutani, M. Expanding role of lenalidomide in hematologic malignancies. Cancer Manag. Res., 2015, 7, 105-119.
[216]
Bianchi, G.; Richardson, P.G.; Anderson, K.C. Promising therapies in multiple myeloma. Blood, 2015, 126, 300-310.
[217]
Naymagon, L.; Abdul-Hay, M. Novel agents in the treatment of multiple myeloma: a review about the future. J. Hematol. Oncol., 2016, 9, 52.
[218]
Rajan, A.M.; Kumar, S. New investigational drugs with single-agent activity in multiple myeloma. Blood Cancer J., 2016, 6, e451.
[219]
Oscio, E.M.; Mitsiades, C.S.; Orlowski, R.Z.; Anderson, K.C. Future agents and treatment directions in multiple myeloma. Expert Rev. Hematol., 2014, 7, 127-141.
[220]
El-Amm, J.; Tabbara, I.A. Emerging therapies in multiple myeloma. Am. J. Clin. Oncol., 2015, 38, 315-321.
[221]
Broijl, A.; Sonneveld, P. An update in the treatment options for multiple myeloma in nontransplant eligible patients. Expert Opin. Pharmacother., 2015, 16, 1945-1957.
[222]
Pratt, G. An oral proteasome inhibitor for multiple myeloma. Lancet Oncol., 2014, 15, 1417-1418.
[223]
Kumar, S.K.; Berdeja, J.G.; Niesvizky, R.; Lonial, S.; Laubach, J.P.; Hamadani, M.; Stewart, A.K.; Hari, P.; Roy, V.; Vescio, R.; Kaufman, J.L.; Berg, D.; Liao, E.; Di Bacco, A.; Estevam, J.; Gupta, N.; Hui, A.M.; Rajkumar, V.; Richardson, P.G. Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Lancet Oncol., 2014, 15, 1503-1512.
[224]
Richardson, P.G.; Baz, R.; Wang, M.; Jakubowiak, A.J.; Laubach, J.P.; Harvey, R.D.; Talpaz, M.; Berg, D.; Liu, G.; Yu, J.; Gupta, N.; Di Bacco, A.; Hui, A.M.; Lonial, S. Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood, 2014, 124, 1038-1046.
[225]
Kumar, S.K.; Bensinger, W.I.; Zimmerman, T.M.; Reeder, C.B.; Berenson, J.R.; Berg, D.; Hui, A.M.; Gupta, N.; Di Bacco, A.; Yu, J.; Shou, Y.; Niesvizky, R. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood, 2014, 124, 1047-1055.
[226]
Richardson, P.G.; Moreau, P.; Laubach, J.P.; Gupta, N.; Hui, A.M.; Anderson, K.C.; San Miguel, J.F.; Kumar, S. The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. Future Oncol., 2015, 11, 1153-1168.
[227]
Gentile, M.; Offidani, M.; Vigna, E.; Corvatta, L.; Recchia, A.G.; Morabito, L.; Morabito, F.; Gentili, S. Ixazomib for the treatment of multiple myeloma. Expert Opin. Investig. Drugs, 2015, 24, 1287-1298.
[228]
Stewart, A.K.; Rajkumar, S.V.; Dimopoulos, M.A.; Masszi, T.; Špička, I.; Oriol, A.; Hájek, R.; Rosiñol, L.; Siegel, D.S.; Mihaylov, G.G.; Goranova-Marinova, V.; Rajnics, P.; Suvorov, A.; Niesvizky, R.; Jakubowiak, A.J.; San-Miguel, J.F.; Ludwig, H.; Wang, M.; Maisnar, V.; Minarik, J.; Bensinger, W.I.; Mateos, M.V.; Ben-Yehuda, D.; Kukreti, V.; Zojwalla, N.; Tonda, M.E.; Yang, X.; Xing, B.; Moreau, P.; Palumbo, A. ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N. Engl. J. Med., 2014, 372, 142-152.
[229]
Sugumar, D.; Keller, J.; Vij, R. Targeted treatments for multiple myeloma: specific role of carfilzomib. Pharmacogenomics Personal Med, 2015, 8, 23-33.
[230]
Muchtar, E.; Gertz, M.A.; Magen, H. A practical review on carfilzomib in multiple myeloma. Eur. J. Haematol., 2016, 96, 564-577.
[231]
Shi, C-X.; Kortűm, K.M.; Zhu, Y.X.; Jedlowski, P.; Bruins, L.; Braggio, E.; Stewart, A.K. Proteasome inhibitors block Ikaros degradation by lenalidomide in multiple myeloma. Haematologica, 2015, 100, e315-e317.
[232]
Atanackovic, D.; Luetkens, T.; Kröger, N. Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma. Leukemia, 2014, 28, 993-1000.
[233]
Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, 12, 252-264.
[234]
Dolan, D.E.; Gupta, S. PD-1 pathway inhibitors: Changing the landscape of cancer immunotherapy. Cancer Contr., 2014, 21, 231-237.
[235]
Philips, G.K.; Atkins, M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int. Immunol., 2014, 27, 39-46.
[236]
List, A.; Kurtin, S.; Roe, D.J.; Buresh, A.; Mahadevan, D.; Fuchs, D.; Rimsza, L.; Heaton, R.; Knight, R.; Zeldis, J.B. Efficacy of lenalidomide in myelodysplastic syndromes. N. Engl. J. Med., 2005, 352, 549-557.
[237]
List, A.; Dewald, G.; Bennett, J.; Giagounidis, A.; Raza, A.; Feldman, E.; Powell, B.; Greenberg, P.; Thomas, D.; Stone, R.; Reeder, C.; Wride, K.; Patin, J.; Schmidt, M.; Zeldis, J.; Knight, R. Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N. Engl. J. Med., 2006, 355, 1456-1465.
[238]
Kuendgen, A.; Lauseker, M.; List, A.F.; Fenaux, P.; Giagounidis, A.A.; Brandenburg, N.A.; Backstrom, J.; Glasmacher, A.; Hasford, J.; Germing, U. International Working Group on MDS with del. (5q). Lenalidomide does not increase AML progression risk in RBC transfusion-dependent patients with low- or intermediate-1-risk MDS with del(5q): A comparative analysis. Leukemia, 2013, 27, 1072-1079.
[239]
List, A.F.; Wride, K.; Dewald, G.; Bennett, J.M.; Giagounidis, A.; Kurtin, S.; Knight, R.D. Cytogenetic response to lenalidomide is associated with improved survival in patients with chromosome 5q deletion. Leuk. Res., 2007, 31 (Suppl. 1), S38, Abstract C028
[240]
Ades, L.; Le Bras, F.; Sebert, M.; Kelaidi, C.; Lamy, T.; Dreyfus, F.; Eclache, V.; Delaunay, J.; Bouscary, D.; Visanica, S.; Turlure, P.; Bresler, A.G.; Cabrol, M.P.; Banos, A.; Blanc, M.; Vey, N.; Delmer, A.; Wattel, E.; Chevret, S.; Fenaux, P. Treatment with lenalidomide does not appear to increase the risk of progression in lower risk myelodysplastic syndromes with 5q deletion. A comparative analysis by the Groupe Francophone des Myelodysplasies. Haematologica, 2012, 97, 213-218.
[241]
List, A.F.; Bennett, J.M.; Sekeres, M.A.; Skikne, B.; Fu, T.; Shammo, J.M.; Nimer, S.D.; Knight, R.D.; Giagounidis, A. MDS- 003 Study Investigators. Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS. Leukemia, 2014, 28, 1033-1040.
[242]
Komrokji, R.S.; List, A.F. Short and long-term benefits of lenalidomide treatment in patients with lower-risk del(5q) myelodysplastic syndromes. Ann. Oncol., 2016, 27, 62-68.
[243]
Giagounidis, A.; Fenaux, P.; Mufti, G.J.; Muus, P.; Platzbecker, U.; Sanz, G.; Cripe, L.; Von Lilienfeld-Toal, M.; Wells, R.A. Practical recommendations on the use of lenalidomide in the management of myelodysplastic syndromes. Ann. Hematol., 2008, 87, 345-352.
[244]
Giagounidis, A.A.; Kulasekararaj, A.; Germing, U.; Radkowski, R.; Haase, S.; Petersen, P.; Göhring, G.; Büsche, G.; Aul, C.; Mufti, G.J.; Platzbecker, U. Long-term transfusion independence in del(5q) MDS patients who discontinue lenalidomide. Leukemia, 2012, 26, 855-858.
[245]
Göhring, G.; Lange, K.; Hofmann, W.; Nielsen, K.V.; Hellström-Lindberg, E.; Roy, L.; Morgan, M.; Kreipe, H.; Büsche, G.; Giagounidis, A.; Schlegelberger, B. Telomere shortening, clonal evolution and disease progression in myelodysplastic syndrome patients with 5q deletion treated with lenalidomide. Leukemia, 2012, 26, 356-358.
[246]
Jädersten, M.; Saft, L.; Pellagatti, A.; Göhring, G.; Wainscoat, J.S.; Boultwood, J.; Porwit, A.; Schlegelberger, B.; Hellström-Lindberg, E. Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. Haematologica, 2009, 94, 1762-1766.
[247]
Jädersten, M.; Saft, L.; Smith, A.; Kulasekararaj, A.; Pomplun, S.; Göhring, G.; Hedlund, A.; Hast, R.; Schlegelberger, B.; Porwit, A.; Hellström-Lindberg, E.; Mufti, G.J. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J. Clin. Oncol., 2011, 29, 1971-1979.
[248]
Kulasekararaj, A.G.; Smith, A.E.; Mian, S.A.; Mohamedali, A.M.; Krishnamurthy, P.; Lea, N.C.; Gäken, J.; Pennaneach, C.; Ireland, R.; Czepulkowski, B.; Pomplun, S.; Marsh, J.C.; Mufti, G.J. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br. J. Haematol., 2013, 160, 660-672.
[249]
Gamez, S.; Ali, A.; Raza, A. Implications of TP53 gene mutations in myelodysplastic syndromes: a review. J. Blood Disorders, 2015, 2, id. 1028.
[250]
Belickova, M.; Vesela, J.; Jonasova, A.; Pejsova, B.; Votavova, H.; Merkerova, M.D.; Zemanova, Z.; Brezinova, J.; Mikulenkova, D.; Lauermannova, M.; Valka, J.; Michalova, K.; Neuwirtova, R.; Cermak, J. TP53 mutation variant allele frequency is a potential predictor for clinical outcome of patients with lower-risk myelodysplastic syndromes. Oncotarget, 2016, 7, 36266-36279.
[251]
Lodé, L.; Ménard, A.; Flet, L.; Richebourg, S.; Loirat, M.; Eveillard, M.; Le Bris, Y.; Godon, C.; Theisen, O.; Gagez, A.L.; Cartron, G.; Commes-Maerten, T.; Villemagne, B.; Luycx, O.; Godmer, P.; Pellat-Deceunynck, C.; Soussi, T.; Béné, M.C.; Delaunay, J.; Peterlin, P. Emergence and evolution of TP53 mutations are a key feature of disease progression in myelodysplastic patients with lower-risk del(5q) treated with lenalidomide. Haematologica, 2018, 103, e143-e146.
[252]
Tehranchi, R.; Woll, P.S.; Anderson, K.; Buza-Vidas, N.; Mizukami, T.; Mead, A.J.; Astrand-Grundström, I.; Strömbeck, B.; Horvat, A.; Ferry, H.; Dhanda, R.S.; Hast, R.; Rydén, T.; Vyas, P.; Göhring, G.; Schlegelberger, B.; Johansson, B.; Hellström-Lindberg, E.; List, A.; Nilsson, L.; Jacobsen, S.E. Persistent malignant stem cells in del(5q) myelodysplasia in remission. N. Engl. J. Med., 2010, 363, 1025-1037.
[253]
Melchert, M.; Kale, V.; List, A. The role of lenalidomide in the treatment of patients with chromosome 5q deletion and other myelodysplastic syndromes. Curr. Opin. Hematol., 2007, 14, 123-129.
[254]
List, A.F. Lenalidomide – The Phoenix Rises. N. Engl. J. Med., 2007, 357, 2183-2186.
[255]
Kurtin, S.E.; List, A.F. Durable long-term responses in patients with myelodysplastic syndromes treated with lenalidomide. Clin. Lymphoma Myeloma, 2009, 9, E10-E13.
[256]
Komrokji, R.S.; List, A.F. Lenalidomide for teatment of myelodysplastic syndromes: current status and future directions. Hematol. Oncol. Clin. North Am., 2010, 24, 377-388.
[257]
Raza, A.; Reeves, J.A.; Feldman, E.J.; Dewald, G.W.; Bennett, J.M.; Deeg, H.J.; Dreisbach, L.; Schiffer, C.A.; Stone, R.M.; Greenberg, P.L.; Curtin, P.T.; Klimek, V.M.; Shammo, J.M.; Thomas, D.; Knight, R.D.; Schmidt, M.; Wride, K.; Zeldis, J.B.; List, A.F. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood, 2008, 111, 86-93.
[258]
Hoefsloot, L.H.; van Amelsvoort, M.P.; Broeders, L.C.; van der Plas, D.C.; van Lom, K.; Hoogerbrugge, H.; Touw, I.P.; Löwenberg, B. Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndrome. Blood, 1997, 89, 1690-1700.
[259]
Santini, V. Anemia as the main manifestation of MDS. Semin. Hematol., 2015, 52, 348-356.
[260]
Sibon, D.; Cannas, G.; Baracco, F.; Prebet, T.; Vey, N.; Banos, A.; Besson, C.; Corm, S.; Blanc, M.; Slama, B.; Perrier, H.; Fenaux, P.; Wattel, E. Groupe Francophone des Myélodysplasies. Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents. Br. J. Haematol., 2012, 156, 619-625.
[261]
Toma, A.; Kosmider, O.; Chevret, S.; Delaunay, J.; Stamatoullas, A.; Rose, C.; Beyne-Rauzy, O.; Banos, A.; Guerci-Bresler, A.; Wickenhauser, S.; Caillot, D.; Laribi, K.; De Renzis, B.; Bordessoule, D.; Gardin, C.; Slama, B.; Sanhes, L.; Gruson, B.; Cony-Makhoul, P.; Chouffi, B.; Salanoubat, C.; Benramdane, R.; Legros, L.; Wattel, E.; Tertian, G.; Bouabdallah, K.; Guilhot, F.; Taksin, A.L.; Cheze, S.; Maloum, K.; Nimuboma, S.; Soussain, C.; Isnard, F.; Gyan, E.; Petit, R.; Lejeune, J.; Sardnal, V.; Renneville, A.; Preudhomme, C.; Fontenay, M.; Fenaux, P.; Dreyfus, F. Lenalidomide with or without erythropoietin in transfusion dependent erythropoiesis-stimulating agent-refractory lower risk MDS without 5q deletion. Leukemia, 2016, 30, 897-905.
[262]
Basiorka, A.A.; Mc Graw, K.L.; De Ceunick, L.; Griner, L.N.; Zhang, L.; Clark, J.A.; Caceres, G.; Sokol, L.; Komrokji, R.S.; Reuther, G.W.; Wei, S.; Tavernier, J.; List, A.F. Lenalidomide stabilizes the erythropoietin receptor by inhibiting the E3 ubiquitin ligase RNF41. Cancer Res., 2016, 76, 3531-3540.
[263]
Jing, X.; Infante, J.; Nachtman, R.G.; Jurecic, R. E3 ligase FLRF (Rnf41) regulates differentiation of hematopoietic progenitors by governing steady – state levels of cytokine and retinoic acid receptors. Exp. Hematol., 2008, 36, 1110-1120.
[264]
Wauman, J.; De Ceunick, L.; Vanderroost, N.; Lievens, S.; Tavernier, J. RNF41 (Nrdp1) controls type 1 cytokine receptor degradation and ectodomain shedding. J. Cell Sci., 2011, 124, 921-932.
[265]
McGraw, K.L.; Fuhler, G.M.; Johnson, J.O.; Clark, J.A.; Caceres, G.C.; Sokol, L.; List, A.F. Erythropoietin receptor signaling is membrane dependent. PLoS One, 2012, 7, e34477.
[266]
McGraw, K.L.; Basiorka, A.A.; Johnson, J.O.; Clark, J.; Caceres, G.; Padron, E.; Heaton, R.; Ozawa, Y.; Wei, S.; Sokol, L.; List, A.F. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors. PLoS One, 2014, 9, e114249.
[267]
Santini, V.; Almeida, A.; Giagounidis, A.; Gröpper, S.; Jonasova, A.; Vey, N.; Mufti, G.J.; Buckstein, R.; Mittelman, M.; Platzbecker, U.; Shpilberg, O.; Ram, R.; Del Cañizo, C.; Gattermann, N.; Ozawa, K.; Risueño, A.; MacBeth, K.J.; Zhong, J.; Séguy, F.; Hoenekopp, A.; Beach, C.L.; Fenaux, P. Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents. J. Clin. Oncol., 2016, 34, 2988-2996.
[268]
Vlachos, A.; Farrar, J.E.; Atsidaftos, E.; Muir, E.; Narla, A.; Markello, T.C.; Singh, S.A.; Landowski, M.; Gazda, H.T.; Blanc, L.; Liu, J.M.; Ellis, S.R.; Arceci, R.J.; Ebert, B.L.; Bodine, D.M.; Lipton, J.M. Diminutive somatic deletions in the 5q region led to a phenotype atypical of clasical 5q- syndrome. Blood, 2013, 122, 2487-2490.
[269]
Ebert, B.L.; Pretz, J.; Bosco, J.; Chang, C.Y.; Tamayo, P.; Galili, N.; Raza, A.; Root, D.E.; Attar, E.; Ellis, S.R.; Golub, T.R. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature, 2008, 451, 252-253.
[270]
Pellagatti, A.; Hellström-Lindberg, E.; Giagounidis, A.; Perry, J.; Malcovati, L.; Della Porta, M.G.; Jädersten, M.; Killick, S.; Fidler, C.; Cazzola, M.; Wainscoat, J.S.; Boultwood, J. Haploinsufficiency of RPS14 in 5q- syndrome is associated with deregulation of ribosomal- and translation-related genes. Br. J. Haematol., 2008, 142, 57-64.
[271]
Sohal, D.; Pellagatti, A.; Zhou, L.; Mo, Y.; Opalinska, J.B.; Alencar, C.; Heuck, C.; Wickrema, A.; Friedman, E.; Greally, J.; Ebert, B.L.; Warner, J.; Boultwood, J.; Verma, A. Downregulation of ribosomal proteins is seen in non 5q- MDS. Blood, 2008, 112, ASH Meeting Abstract 854.
[272]
Wu, L.; Li, X.; Xu, F.; Zhang, Z.; Chang, C.; He, Q. Low RPS14 expression in MDS without 5q- aberration confers higher apoptosis rate of nucleated erythrocytes and predicts prolonged survival and possible response to lenalidomide in lower risk non-5q- patients. Eur. J. Haematol., 2013, 90, 486-493.
[273]
Czibere, A.G.; Bruns, I.; Junge, B.; Singh, R.; Kobbe, G.; Haas, R.; Germing, U. Low RPS14 expression is common in myelodysplastic syndromes without 5q- aberration and defines a subgroup of patients with prolonged survival. Haematologica, 2009, 94, 1453-1455.
[274]
Dutt, S.; Narla, A.; Lin, K.; Mullally, A.; Abayasekara, N.; Megerdichian, C.; Wilson, F.H.; Currie, T.; Khanna-Gupta, A.; Berliner, N.; Kutok, J.L.; Ebert, B.L. Haploinsufficiency for ribosomal protein genes causes selective activation of p53 in human erythroid progenitor cells. Blood, 2011, 117, 2567-2576.
[275]
Zhang, Y.; Lu, H. Signaling to p53: ribosomal proteins find their way. Cancer Cell, 2009, 16, 369-377.
[276]
Fumagalli, S.; Di Cara, A.; Neb-Gulati, A.; Natt, F.; Schwemberger, S.; Hall, J.; Babcock, G.F.; Bernardi, R.; Pandolfi, P.P.; Thomas, G. Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11-translation-dependent mechanism of p53 induction. Nat. Cell Biol., 2009, 11, 501-508.
[277]
Pellagatti, A.; Marafioti, T.; Paterson, J.C.; Barlow, J.L.; Drynan, L.F.; Giagounidis, A.; Pileri, S.A.; Cazzola, M.; McKenzie, A.N.; Wainscoat, J.S.; Boultwood, J. Induction of p53 and up-regulation of the p53 pathway in the human 5q- syndrome. Blood, 2010, 115, 2721-2723.
[278]
Danilova, N.; Kumagai, A.; Lin, J. p53 upregulation is a frequent response to deficiency of cell-essential genes. PLoS One, 2010, 5, e15938.
[279]
Fumagalli, S.; Thomas, G. The role of p53 in ribosomopathies. Semin. Hematol., 2011, 48, 97-105.
[280]
Cazzola, M. Myelodysplastic syndrome with isolated 5q deletion (5q- syndrome). A clonal stem cell disorder characterized by defective ribosome biogenesis. Haematologica, 2008, 93, 967-972.
[281]
Barlow, J.L.; Drynan, L.F.; Trim, N.L.; Erber, W.N.; Warren, A.J.; McKenzie, A.N. New insights into 5q- syndrome as a ribosomopathy. Cell Cycle, 2010, 9, 4286-4293.
[282]
Ebert, B.L. Deletion 5q in myelodysplastic syndrome: a paradigm for the study of hemizygous deletions in cancer. Leukemia, 2009, 23, 1252-1256.
[283]
Narla, A.; Ebert, B.L. Ribosomopathies: human disorders of ribosome dysfunction. Blood, 2010, 115, 3196-3205.
[284]
Ebert, B.L.; Galili, N.; Tamayo, P.; Bosco, J.; Mak, R.; Pretz, J.; Tanguturi, S.; Ladd-Acosta, C.; Stone, R.; Golub, T.R.; Raza, A. An erythroid differentiation signature predicts response to lenalidomide in myelodysplastic syndrome. PLoS Med., 2008, 5, e35.
[285]
Kerdivel, G.; Chesnais, V.; Becht, E.; Toma, A.; Cagnard, N.; Dumont, F.; Rousseau, A.; Fenaux, P.; Chevret, S.; Chapuis, N.; Boeva, V.; Fridman, W.H.; Fontenay, M.; Kosmider, O. Lenalidomide-mediated erythroid improvement in non-del(5q) Myelodysplastic syndromes is associated with bone marrow immuno-remodeling. Leukemia, 2018, 32, 558-562.
[286]
Adès, L.; Boehrer, S.; Prebet, T.; Beyne-Rauzy, O.; Legros, L.; Ravoet, C.; Dreyfus, F.; Stamatoullas, A.; Chaury, M.P.; Delaunay, J.; Laurent, G.; Vey, N.; Burcheri, S.; Mbida, R.M.; Hoarau, N.; Gardin, C.; Fenaux, P. Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study. Blood, 2009, 113, 3947-3952.
[287]
Cheson, B.D.; Greenberg, P.L.; Bennett, J.M.; Lowenberg, B.; Wijermans, P.W.; Nimer, S.D.; Pinto, A.; Beran, M.; de Witte, T.M.; Stone, R.M.; Mittelman, M.; Sanz, G.F.; Gore, S.D.; Schiffer, C.A.; Kantarjian, H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood, 2006, 108, 419-425.
[288]
Möllgård, L.; Saft, L.; Treppendahl, M.B.; Dybedal, I.; Nørgaard, J.M.; Astermark, J.; Ejerblad, E.; Garelius, H.; Dufva, I.H.; Jansson, M.; Jädersten, M.; Kjeldsen, L.; Linder, O.; Nilsson, L.; Vestergaard, H.; Porwit, A.; Grønbæk, K.; Hellström-Lindberg, E. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. Haematologica, 2011, 96, 963-971.
[289]
Fenaux, P.; Giagounidis, A.; Selleslag, D.; Beyne-Rauzy, O.; Mufti, G.J.; Mittelman, M.; Muus, P.; te Boekhorst, P.; Sanz, G.; del Canizo, C.; Guerci-Bresler, A.; Schlegelberger, B.; Aul, C.; Kreipe, H.; Goehring, G.; Knight, R.; Francis, J.; Fu, T.; Hellström-Lindberg, E. RBC transfusion independence and safety profile of lenalidomide 5 or 10 mg in pts with low- or int-1-risk MDS with del5q: results from a randomized phase III trial (MDS-004). Blood, 2009, 114, ASH Abstract 944.
[290]
Fenaux, P.; Giagounidis, A.; Selleslag, D.; Beyne-Rauzy, O.; Mittelman, M.; Muus, P.; Knight, R.D.; Fu, T.; Hellstrom-Lindberg, E. Safety of lenalidomide (LEN) from a randomized phase III trial (MDS-004) in low-/int-1-risk myelodysplastic syndromes (MDS) with a del(5q) abnormality. J. Clin. Oncol., 2010, 28(Suppl.), 6598.
[291]
Fenaux, P.; Giagounidis, A.; Selleslag, D.; Beyne-Rauzy, O.; Mufti, G.; Mittelman, M.; Muus, P.; Te Boekhorst, P.; Sanz, G.; Del Cañizo, C.; Guerci-Bresler, A.; Nilsson, L.; Platzbecker, U.; Lübbert, M.; Quesnel, B.; Cazzola, M.; Ganser, A.; Bowen, D.; Schlegelberger, B.; Aul, C.; Knight, R.; Francis, J.; Fu, T.; Hellström-Lindberg, E. MDS-004 Lenalidomide del5q Study Group. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low-/intermediate-1-risk myelodysplastic syndromes with del5q. Blood, 2011, 118, 3765-3776.
[292]
Sekeres, M.A. Lenalidomide in MDS: 4th time’s a charm. Blood, 2011, 118, 3757-3758.
[293]
Revicki, D.A.; Brandenburg, N.A.; Muus, P.; Yu, R.; Knight, R.; Fenaux, P. Health-related quality of life outcomes of lenalidomide in transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndromes with a chromosome 5q deletion: results from a randomized clinical trial. Leuk. Res., 2013, 37, 259-265.
[294]
Le Bras, F.; Sebert, M.; Kelaidi, C.; Lamy, T.; Dreyfus, F.; Delaunay, J.; Banos, A.; Blanc, M.; Vey, N.; Schmidt, A.; Visanica, S.; Eclache, V.; Turlure, P.; Beyne-Rauzy, O.; Guerci, A.; Delmer, A.; de Botton, S.; Rea, D.; Fenaux, P.; Adès, L. Treatment by lenalidomide in lower risk myelodysplastic syndrome with 5q deletion-the GFM experience. Leuk. Res., 2011, 35, 1444-1448.
[295]
Cheson, B.D.; Bennett, J.M.; Kantarjian, H.; Pinto, A.; Schiffer, C.A.; Nimer, S.D.; Löwenberg, B.; Beran, M.; de Witte, T.M.; Stone, R.M.; Mittelman, M.; Sanz, G.F.; Wijermans, P.W.; Gore, S.; Greenberg, P.L. World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood, 2000, 96, 3671-3674.
[296]
Tiu, R.V.; Sekeres, M.A. Lenalidomide in del 5q MDS: Responses and side effects revisited. Leuk. Res., 2011, 35, 1440-1441.
[297]
Harada, H.; Watanabe, M.; Suzuki, K.; Yanagita, S.; Suzuki, T.; Yoshida, Y.; Kimura, A.; Tsudo, M.; Matsuda, A.; Tohyama, K.; Taniwaki, M.; Takeshita, K.; Takatoku, M.; Ozawa, K. Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes with a deletion 5q abnormality. Int. J. Hematol., 2009, 90, 353-360.
[298]
Matsuda, A.; Taniwaki, M.; Jinnai, I.; Harada, H.; Watanabe, M.; Suzuki, K.; Yanagita, S.; Suzuki, T.; Yoshida, Y.; Kimura, A.; Tsudo, M.; Tohyama, K.; Takatoku, M.; Ozawa, K. Morphologic analysis in myelodysplastic syndromes with del(5q) treated with lenalidomide. A Japanese multiinstitutional study. Leuk. Res., 2012, 36, 575-580.
[299]
Sánchez-Garcia, J.; del Canizo, C. Lorenzo, I.; Nomdedeu, B.; Luño, E.; de Paz, R.; Xicoy, B.; Valcárcel, D.; Brunet, S.; Marco-Betes, V.; García-Pintos, M.; Osorio, S.; Tormo, M.; Bailén, A.; Cerveró, C.; Ramos, F.; Diez-Campelo, M.; Such, E.; Arrizabalaga, B.; Azaceta, G.; Bargay, J.; Arilla, M.J.; Falantes, J.; Serrano-López, J.; Sanz, G.F.; Spanish Group on Myelodysplastic Syndromes (GES MD). Multivariate time-dependent comparison of the impact of lenalidomide in lower-risk myelodysplastic syndromes with chromosome 5q deletion. Br. J. Haematol., 2014, 166, 189-201.
[300]
Cerqui, E.; Pelizzari, A.; Schieppati, F.; Borlenghi, E.; Pagani, C.; Bellotti, D.; Lamorgese, C.; Boiocchi, L.; Sottini, A.; Imberti, L.; Rossi, G. Lenalidomide in patients with red blood cell transfusion-dependent myelodysplastic syndrome and del(5q): a single-centre “real-world” experience. Leuk. Lymphoma, 2015, 56, 3129-3134.
[301]
Sharma, S.V.; Lee, D.Y.; Li, B.; Quinlan, M.P.; Takahashi, F.; Maheswaran, S.; McDermott, U.; Azizian, N.; Zou, L.; Fischbach, M.A.; Wong, K.K.; Brandstetter, K.; Wittner, B.; Ramaswamy, S.; Classon, M.; Settleman, J. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell, 2010, 141, 69-80.
[302]
Giagounidis, A.A.N. Lenalidomide for del(5q) and non-del(5q) myelodysplastic syndromes. Semin. Hematol., 2012, 49, 312-322.
[303]
List, A.F.; Lancet, J.E.; Melchert, M.; Lush, R.; Yu, J.; Chen, N.; Schmidt, M.; Knight, R. Two-stage pharmacokinetic efficacy study of lenalidomide alone or combined with recombinant erythropoietin (EPO) in lower risk MDS EPO-failures [PK-002]. Blood, 2007, 110, ASH Meeting Abstract 4626.
[304]
Park, S.; Vassilieff, D.; Bardet, V.; Viguié, F.; Dreyfus, F. Efficacy of the association of lenalidomide to erythropoiesis-stimulating agents in del (5q) MDS patients refractory to single-agent lenalidomide. Leukemia, 2010, 24, 1960-1977.
[305]
Emanuel, P.D.; Wang, Z.; Cai, D. TLK199 (TelintraTM), a novel glutathione analog inhibitor of GST P1-1, causes proliferation and maturation of bone marrow precursor cells and correlates with clinical improvement in myelodysplastic syndrome (MDS) patients in a phase 2a study. Blood, 2004, 104, ASH Meeting Abstract 2372.
[306]
Galili, N.; Tamayo, P.; Botvinnik, O.B.; Mesirov, J.P.; Brooks, M.R.; Brown, G.; Raza, A. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J. Hematol. Oncol., 2012, 5, 20.
[307]
Raza, A.; Galili, N.; Smith, S.; Godwin, J.; Lancet, J.; Melchert, M.; Jones, M.; Keck, J.G.; Meng, L.; Brown, G.L.; List, A. Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199 tablets), a novel glutathione analog prodrug, in patients with myelodysplastic syndrome. Blood, 2009, 113, 6533-6540.
[308]
Raza, A.; Galili, N.; Callander, N.; Ochoa, L.; Piro, L.; Emanuel, P.; Williams, S.; Burris, H., III; Faderl, S.; Estrov, Z.; Curtin, P.; Larson, R.A.; Keck, J.G.; Jones, M.; Meng, L.; Brown, G.L. Phase 1-2a multicenter dose-escalastion study of ezatiostat hydrochloride liposomes for injection (Telintra, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome. J. Hematol. Oncol., 2009, 2, 20.
[309]
Quddus, F.; Clima, J.; Seedham, H.; Sajjad, G.; Galili, N.; Raza, A. Oral ezatiostat HCl (TLK199) and myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure. J. Hematol. Oncol., 2010, 3, 16.
[310]
Raza, A.; Galili, N.; Mulford, D.; Smith, S.E.; Brown, G.L.; Steensma, D.P.; Lyons, R.M.; Boccia, R.; Sekeres, M.A.; Garcia-Manero, G.; Mesa, R.A. Phase 1 dose-ranging study of oral ezatiostat hydrochloride (Telintra, TLK 199) in combination with lenalidomide (Revlimid) in patients with non-deletion(5q) low to intermediate-1 risk myelodysplastic syndrome (MDS). J. Hematol. Oncol., 2012, 5, 18.
[311]
Lyons, R.M.; Wilks, S.T.; Young, S.; Brown, G.L. Oral ezatiostat HCL (Telintra, TLK 199) and idiopathic chronic neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. J. Hematol. Oncol., 2011, 4, 43.
[312]
Raza, A.; Galili, N.; Smith, S.E.; Godwin, J.; Boccia, R.V.; Myint, H.; Mahadevan, D.; Mulford, D.; Rarick, M.; Brown, G.L.; Schaar, D.; Faderl, S.; Komrokji, R.S.; List, A.F.; Sekeres, M. A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome. Cancer, 2012, 118, 2138-2147.
[313]
Sekeres, M.A.; List, A.F.; Cuthbertson, D.; Paquette, R.; Ganetzky, R.; Latham, D.; Paulic, K.; Afable, M.; Saba, H.I.; Loughran, T.P. Jr.; Maciejewski, J.P. Phase I combination trial of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes. J. Clin. Oncol., 2010, 28, 2253-2258.
[314]
Sekeres, M.A.; O’Keefe, C.; List, A.F.; Paulic, K.; Afable, M., II; Englehaupt, R.; Maciejewski, J.P. Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher-risk myelodysplastic syndromes. Am. J. Hematol., 2011, 86, 102-103.
[315]
Garcia-Manero, G.; Daver, N.G.; Borthakur, G.; Konopleva, M.; Ravandi, F.; Wierda, W.G.; Estrov, Z.; Faderl, S.; Kadia, T.; Rey, K.; Cheung, C.; Kantarjian, H.M. Phase I study of the combination of 5-azacitidine sequentially with high-dose lenalidomide in higher-risk myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Blood, 2011, 118, ASH Meeting Abstract 2613.
[316]
Bally, C.; Itzykson, R.; Gruson, B.; Dreyfus, F.; Siguret, V.; Taksin, A.L.; de Renzis, B.; Legros, L.; Thomas, X.; Bouabdallah, K.; Chaibi, P.; Kelaidi, C.; Fenaux, P.; Ades, L. Azacitidine (AZA) after failure of lenalidomide (LEN) in low/int-1 risk MDS with del 5q. Blood, 2011, 118, ASH Meeting Abstract 2786
[317]
Platzbecker, U.; Ganster, C.; Neesen, J.; Kuendgen, A.; Götze, K.; Bug, G.; Shirneshan, K.; Braulke, F.; Röllig, C.; Naumann, R.; Bűssemaker, E.; Giagounidis, A.; Hofmann, W.K.; Germing, U.; vHaase, D.; Ehninger, G. Safety and efficacy of a combination of 5-azacitidine followed by lenalidomide in high-risk MDS or AML patients with del(5q) cytogenetic abnormalities-results of the “AZALE” trial. Blood, 2011, 118, ASH Meeting Abstract 3799
[318]
Wei, A.H.; Tan, P.T.; Walker, P.A.; Avery, S.; Patil, S.S.; Schwarer, A.P.; Janusewicz, E.; Harrison, S.J.; Ho, W.K.; Tam, C.S.; Spencer, A. A phase Ib dose escalation safety analysis of lenalidomide and azacitidine maintenance therapy for poor risk AML.Blood, 2011, 118, ASH Meeting Abstract 3625
[319]
Sekeres, M.A.; Tiu, R.V.; Komrokji, R.; Lancet, J.; Advani, A.S.; Afable, M.; Englehaupt, R.; Juersivich, J.; Cuthbertson, D.; Paleveda, J.; Tabarroki, A.; Visconte, V.; Makishima, H.; Jerez, A.; Paquette, R.; List, A.F.; Maciejewski, J.P. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood, 2012, 120, 4945-4951.
[320]
Pollyea, D.A.; Kohrt, H.E.; Gallegos, L.; Figueroa, M.E.; Abdel-Wahab, O.; Zhang, B.; Bhattacharya, S.; Zehnder, J.; Liedtke, M.; Gotlib, J.R.; Coutre, S.; Berube, C.; Melnick, A.; Levine, R.; Mitchell, B.S.; Medeiros, B.C. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia, 2012, 26, 893-901.
[321]
Scherman, E.; Malak, S.; Perot, C.; Gorin, N.C.; Rubio, M.T.; Isnard, F. Interest of the association azacitidine-lenalidomide as frontline therapy in high-risk myelodysplasia or acute myeloid leukemia with complex karyotype. Leukemia, 2012, 26, 822-824.
[322]
Pollyea, D.A.; Zehnder, J.; Coutre, S.; Pollyea, D.A.; Zehnder, J.; Coutre, S. Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica, 2013, 98, 591-596.
[323]
Platzbecker, U.; Germing, U. Combination of azacitidine and lenalidomide in myelodysplastic syndromes or acute myeloid leukemia-a wise liason? Leukemia, 2013, 27, 1813-1819.
[324]
Zeidan, A.M.; Gore, S.D.; Komrokji, R.S. Higher-risk myelodysplastic syndromes with del(5q): is sequential azacitidine-lenalidomide combination the way to go? Expert Rev. Hematol., 2013, 6, 251-254.
[325]
Ramsingh, G.; Westervelt, P.; Cashen, A.F.; Uy, G.L.; Stockerl-Goldstein, K.; Abboud, C.N.; Bernabe, N.; Monahan, R.; DiPersio, J.F.; Vij, R. A phse 1study of concomitant high-dose lenalidomide and 5- azacitidine induction in the treatment of AML. Leukemia, 2013, 27, 725-728.
[326]
Ornstein, M.C.; Mukherjee, S.; Sekeres, M.A. More is better: Combination therapies for myelodysplastic syndromes. Best Pract. Res. Clin. Haematol., 2015, 28, 22-31.
[327]
Wei, A.; Tan, P.; Perruzza, S.; Govindaraj, C.; Fleming, S.; McManus, J.; Avery, S.; Patil, S.; Stevenson, W.; Plebanski, M.; Spencer, A. Maintenance lenalidomide in combination with 5-azacitidine as post-remision therapy for acute myeloid leukemia. Br. J. Haematol., 2015, 169, 199-210.
[328]
Ganster, C.; Shirneshan, K.; Salinas-Riester, G.; Braulke, F.; Schanz, J.; Platzbecker, U.; Haase, D. Influence of total genomic alteration and chromosomal fragmentation on response to a combination of azacitidine and lenalidomide in a cohort of patients with very high risk MDS. Leuk. Res., 2015, 39, 1079-1087.
[329]
Todaro, J.; Weinschenker-Bollmann, P.; Rother, E.T.; del Giglio, A. Azacitidine and lenalidomide as an alternative treatment for refractory acute myeloid leukemia: a case report. Sao Paulo Med. J., 2015, 133, 271-274.
[330]
Narayan, R.; Garcia, J.S.; Percival, M.E.M.; Berube, C.; Coutre, S.; Gotlib, J.; Greenberg, P.; Liedtke, M.; Hewitt, R.; Regan, K.; Williamson, C.; Doykan, C.; Cardone, M.H.; McMillan, A.; Medeiros, B.C. Sequential azacitidine plus lenalidomide in previously treated elderly patients with acute myeloid leukemia and higher risk myelodysplastic syndrome. Leuk. Lymphoma, 2016, 57, 609-615.
[331]
Finelli, C.; Clissa, C.; Follo, M.; Stanzani, M.; Parisi, S.; Mongiorgi, S.; Barraco, M.; Avanziani, P.; Bosi, C.; Castagnazi, B.; Candoni, A.; Crugnola, M.; Giannini, M.B.; Gobbi, M.; Leonardi, G.; Rigolin, G.M.; Russo, D.; Tosi, P.; Visani, G.; Cocco, L.; Cavo, M. Azacitidine and lenalidomide (combined vs sequential treatment in higher-risk myelodysplastic syndromes. Long-term results of a randomized phase II multicenter study. Blood, 2016, 128, ASH Meeting Abstract 3169
[332]
Broudy, V.C.; Lin, N.L. AMG 531 stimulates megakaryopoiesis in vitro by binding to Mpl. Cytokine, 2004, 25, 52-60.
[333]
Wang, B.; Nichol, J.L.; Sullivan, J.T. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin. Pharmacol. Ther., 2004, 76, 628-638.
[334]
Frampton, J.E.; Lyseng-Williamson, K.A. Romiplostim. Drugs, 2009, 69, 307-317.
[335]
Keating, G.M. Romiplostim: a review of its use in immune thrombocytopenia. Drugs, 2012, 72, 415-435.
[336]
Kantarjian, H.; Fenaux, P.; Sekeres, M.; Becker, P.S.; Boruchov, A.; Bowen, D.; Hellstrom-Lindberg, E.; Larson, R.A.; Lyons, R.M.; Muus, P.; Shammo, J.; Siegel, R.; Hu, K.; Franklin, J.; Berger, D.P. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J. Clin. Oncol., 2010, 28, 437-444.
[337]
Wang, E.S.; Lyons, R.M.; Larson, R.A.; Gandhi, S.; Liu, D.; Matei, C.; Scott, B.; Hu, K.; Yang, A.S. A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide. J. Hematol. Oncol., 2012, 5, 71.
[338]
Narla, A.; Dutt, S.; McAuley, R.J.; Al-Shahrour, F.; Hurst, S.; McConkey, M.; Neuberg, D.; Ebert, B.L. Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis. Blood, 2011, 118, 2296-2304.
[339]
Komrokji, R.S.; Al Ali, N.H.; Padron, E.; Lee, J.H.; Hillgruber, N.; Tinsley, S.; Lancet, J.E.; List, A. A phase II clinical trial of lenalidomide and prednisone in low and intermediate-1 IPSS risk, non-del(5q) MDS patients. Blood, 2013, 122, ASH Meeting Abstract 1506
[340]
Jonasova, A.; Neuwirtova, R.; Polackova, H.; Siskova, M.; Stopka, T.; Cmunt, E.; Belickova, M.; Moudra, A.; Minarik, L.; Fuchs, O.; Michalova, K.; Zemanova, Z. Lenalidomide treatment in lower risk myelodysplastic syndromes-The experience of a Czech hematology center (Positive effect of erythropoietin ±prednisone addition nto lenalidomide in refractory or relapsed patients). Leuk. Res., 2018, 69, 12-17.
[341]
Cmejlova, J.; Dolezalova, L.; Pospisilova, D.; Petrtylova, K.; Petrak, J.; Cmejla, R. Translational efficiency in patients with Diamond-Blackfan anemia. Haematologica, 2006, 91, 1456-1464.
[342]
Pospisilova, D.; Cmejlova, J.; Hak, J.; Adam, T.; Cmejla, R. Successful treatment of a Diamond-Blackfan anemia patient with amino acid leucine. Haematologica, 2007, 92, e66-e67.
[343]
Payne, E.; Virgilio, M.; Narla, A.; Sun, H.; Levine, M.; Paw, B.H.; Berliner, N.; Look, A.T.; Ebert, B.L.; Khanna-Gupta, A. L-leucine improves anemia and developmental defects associated with Diamond-Blackfan anemia and del(5q) MDS by activating the mTOR pathway. Blood, 2012, 120, 2214-2224.
[344]
Yip, B.H.; Pellagatti, A.; Vuppusetty, C.; Giagounidis, A.; Germing, U.; Lamikanra, A.A.; Roberts, D.J.; Fernandez-Mercado, M.; McDonald, E.J.; Killick, S.; Wainscoat, J.S.; Boultwood, J. Effects of L-leucine in 5q- syndrome and other RPS14-deficient erythroblasts. Leukemia, 2012, 26, 2154-2158.
[345]
Heise, C.; Carter, T.; Schafer, P.; Chopra, R. Pleiotropic mechanisms of action of lenalidomide efficacy in del(5q) myelodysplastic syndromes. Expert Rev. Anticancer Ther., 2010, 10, 1663-1672.
[346]
Voutsadakis, I.A.; Cairoli, A. A critical review of the molecular pathophysiology of lenalidomide sensitivity in 5q- myelodysplastic syndromes. Leuk. Lymphoma, 2012, 53, 779-788.
[347]
Wei, S.; Chen, X.; Rocha, K.; Epling-Burnette, P.K.; Djeu, J.Y.; Liu, Q.; Byrd, J.; Sokol, L.; Lawrence, N.; Pireddu, R.; Dewald, G.; Williams, A.; Maciejewski, J.; List, A. A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc. Natl. Acad. Sci. USA, 2009, 106, 12974-12979.
[348]
Moutouh-de Parseval, L.A.; Verhelle, D.; Glezer, E.; Jensen-Pergakes, K.; Ferguson, G.D.; Corral, L.G.; Morris, C.L.; Muller, G.; Brady, H.; Chan, K. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells. J. Clin. Invest., 2008, 118, 248-258.
[349]
Fuchs, O. Important genes in the pathogenesis of 5q- syndrome and their connection with ribosomal stress and the innate immune system pathway. Leukemia Res. Treat., 2012, 2012, 179402.
[350]
Bursac, S.; Brdovcak, M.C.; Pfannkuchen, M.; Orsolić, I.; Golomb, L.; Zhu, Y.; Katz, C.; Daftuar, L.; Grabušić, K.; Vukelić, I.; Filić, V.; Oren, M.; Prives, C.; Volarevic, S. Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress. Proc. Natl. Acad. Sci. USA, 2012, 109, 20467-20472.
[351]
Wei, S.; Chen, X.; McGraw, K.; Zhang, L.; Komrokji, R.; Clark, J.; Caceres, G.; Billingsley, D.; Sokol, L.; Lancet, J.; Fortenbery, N.; Zhou, J.; Eksioglu, E.A.; Sallman, D.; Wang, H.; Epling-Burnette, P.K.; Djeu, J.; Sekeres, M.; Maciejewski, J.P.; List, A. Lenalidomide promotes p53 degradation by inhibiting MDM2 autoubiquitination in myelodysplastic syndrome with chromosome 5q deletion. Oncogene, 2013, 32, 1110-1120.
[352]
Escoubet-Lozach, L.; Lin, I.L.; Jensen-Pergakes, K.; Brady, H.A.; Gandhi, A.K.; Schafer, P.H.; Muller, G.W.; Worland, P.J.; Chan, K.W.; Verhelle, D. Pomalidomide and lenalidomide induce p21 WAF-1 expression in both lymphoma and multiple myeloma through a LSD1 mediated epigenetic mechanism. Cancer Res., 2009, 69, 7347-7356.
[353]
Fisher, J.W. Erythropoietin: physiology and pharmacology update. Exp. Biol. Med. (Maywood), 2003, 228, 1-14.
[354]
Perreault, A.A.; Venters, B.J. Integrative view on how erythropoietin signaling controls transcription patterns in erythroid cells. Curr. Opin. Hematol., 2018, 25, 189-195.
[355]
Hennighausen, L.; Robinson, G.W. Interpretation of cytokine signaling through in the transcription factors STAT5A and STAT5B. Genes Dev., 2008, 22, 711-721.
[356]
List, A.; Estes, M.; Williams, A.; Sekharam, M.; Ozawa, U.; Gao, G.; Wu, J.; Gao, G.; Sokol, L. Lenalidomide (CC-5013; Revlimid) promotes erythropoiesis in myelodysplastic syndromes by CD45 protein tyrosine phosphatase inhibition. Blood, 2006, 108, ASH Meeting Abstract 1360.
[357]
Warlick, E.D.; Miller, J.S. Myelodysplastic syndromes: the role of the immune system in pathogenesis. Leuk. Lymphoma, 2011, 52, 2045-2049.
[358]
Braun, T.; Fenaux, R. Myelodysplastic syndromes (MDS) and autoimmune disorders (AD): cause or consequence? Best Pract. Res. Clin. Haematol., 2013, 26, 327-336.
[359]
Gañán-Gómez, I.; Wei, Y.; Starczynowski, D.T.; Colla, S.; Yang, H.; Cabrero-Calvo, M.; Bohannan, Z.S.; Verma, A.; Steidl, U.; Garcia-Manero, G. Deregulation of innate immune and inflammatory signaling in myelodysplastic syndromes. Leukemia, 2015, 29, 1458-1469.
[360]
Varney, M.E.; Melgar, K.; Niederkorn, M.; Smith, M.; Barreyro, L.; Starczynowski, D.T. Deconstructing innate immune signaling in myelodysplastic syndromes. Exp. Hematol., 2015, 43, 587-598.
[361]
Wolach, O.; Stone, R. Autoimmunity and inflammation in myelodysplastic syndromes. Acta Haematol., 2016, 136, 108-117.
[362]
Fuchs, O. The immune mechanisms involved in the pathogenesis and pathophysiology of myelodysplastic syndromes and immunotherapeutic strategies. J. Hematol. Hemother., 2016, 1, 001.
[363]
Fozza, C. The burden of autoimmunity in myelodysplastic syndromes. Hematol. Oncol., 2018, 36, 15-23.
[364]
Epling-Burnette, P.K.; List, A.F. Advancements in the molecular pathogenesis of myelodysplastic syndrome. Curr. Opin. Hematol., 2009, 16, 70-76.
[365]
Epling-Burnette, P.K.; Painter, J.S.; Rollison, D.E.; Ku, E.; Vendron, D.; Widen, R.; Boulware, D.; Zou, J.X.; Bai, F.; List, A.F. Prevalence and clinical association of clonal T cell expansions in myelodysplastic syndrome. Leukemia, 2007, 21, 659-667.
[366]
Pellagatti, A.; Boultwood, J. Recent advances in the 5q- syndrome. Mediterr. J. Hematol. Infect. Dis., 2015, 7, e2015037.
[367]
Schafer, P.H.; Gandhi, A.K.; Loveland, M.A.; Chen, R.S.; Man, H.W.; Schnetkamp, P.P.; Wolbring, G.; Govinda, S.; Corral, L.G.; Payvandi, F.; Muller, G.W.; Stirling, D.I. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J. Pharmacol. Exp. Ther., 2003, 305, 1663-1672.
[368]
Zhu, D.; Corral, L.G.; Fleming, Y.W.; Stein, B. Immunomodulatory drugs Revlimid (Lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. Cancer Immunol. Immunother., 2008, 57, 1849-1859.
[369]
Chang, D.H.; Liu, N.; Klimek, V.; Hassoun, H.; Mazumder, A.; Nimer, S.D.; Jagannath, S.; Dhodapkar, M.V. Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood, 2006, 108, 618-621.
[370]
Starczynowski, D.T.; Kuchenbauer, F.; Argiropoulos, B.; Sung, S.; Morin, R.; Muranyi, A.; Hirst, M.; Hogge, D.; Marra, M.; Wells, R.A.; Buckstein, R.; Lam, W.; Humphries, R.K.; Karsan, A. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat. Med., 2010, 16, 49-58.
[371]
Starczynowski, D.T.; Karsan, A. Deregulation of innate immune signaling in myelodysplastic syndromes is associated with deletion of chromosome arm 5q. Cell Cycle, 2010, 9, 855-856.
[372]
Starczynowski, D.T.; Karsan, A. Innate immune signaling in the myelodysplastic syndromes. Hematol. Oncol. Clin. North Am., 2010, 24, 343-359.
[373]
Rhyasen, G.W.; Starczynowski, D.T. Deregulation of microRNAs in myelodysplastic syndrome. Leukemia, 2012, 26, 13-22.
[374]
Fang, J.; Varney, M.; Starczynowski, D.T. Implication of microRNAs in the pathogenesis of MDS. Curr. Pharm. Des., 2012, 18, 3170-3179.
[375]
Fang, J.; Barker, B.; Bolanos, L.; Liu, X.; Jerez, A.; Makishima, H.; Christie, S.; Chen, X.; Rao, D.S.; Grimes, H.L.; Komurov, K.; Weirauch, M.T.; Cancelas, J.A.; Maciejewski, J.P.; Starczynowski, D.T. Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-κB gene network. Cell Reports, 2014, 8, 1328-1338.
[376]
Merkerova, M.D.; Krejcik, Z.; Belickova, M.; Hrustincova, A.; Klema, J.; Stara, E.; Zemanova, Z.; Michalova, K.; Cermak, J.; Jonasova, A. Genome-wide miRNA profiling in myelodysplastic syndrome with del(5q) treated with lenalidomide. Eur. J. Haematol., 2015, 95, 35-43.
[377]
Varney, M.E.; Niederkorn, M.; Konno, H.; Matsumura, T.; Gohda, J.; Yoshida, N.; Akiyama, T.; Christie, S.; Fang, J.; Miller, D.; Jerez, A.; Karsan, A.; Maciejewski, J.P.; Meetei, R.A.; Inoue, J.; Starczynowski, D.T. Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling. J. Exp. Med., 2015, 212, 1967-1985.
[378]
Oliva, E.N.; Cuzzola, M.; Nobile, F.; Ronco, F.; D’Errigo, M.G.; Laganà, C.; Morabito, F.; Galimberti, S.; Cortelezzi, A.; Aloe-Spiriti, M.A.; Specchia, G.; Poloni, A.; Breccia, M.; Ghio, R.; Finelli, C.; Iacopino, P.; Alimena, G.; Latagliata, R. Changes in RPS 14 expression levels during lenalidomide treatment in low and intermediate-1-risk myelodysplastic syndromes with chromosome 5q deletion. Eur. J. Haematol., 2010, 85, 231-235.
[379]
Oliva, E.N.; Cuzzola, M.; Aloe-Spiriti, M.A.; Poloni, A.; Laganà, C.; Rigolino, C.; Morabito, F.; Galimberti, S.; Ghio, R.; Cortelezzi, A.; Palumbo, G.A.; Sanpaolo, G.; Finelli, C.; Ricco, A.; Volpe, A.; Rodà, F.; Breccia, M.; Alimena, G.; Nobile, F.; Latagliata, R. Biological activity of lenalidomide in myelodysplastic syndromes with del5q: results of gene expression profiling from a multicenter phase II study. Ann. Hematol., 2013, 92, 25-32.
[380]
Venner, C.P.; Wegrzyn-Woltosz, J.; Nevill, T.J.; Deeg, H.J.; Caceres, G.; Platzbecker, U.; Scott, B.L.; Sokol, L.; Sung, S.; List, A.F.; Karsan, A. Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34+ cells from patients with del(5q) myelodysplastic syndrome. Haematologica, 2013, 98, 409-413.
[381]
Min, Y.; Wi, S.M.; Kang, J.A.; Yang, T.; Park, C.S.; Park, S.G.; Chung, S.; Shim, J.H.; Chun, E.; Lee, K.Y. Cereblon negatively regulates TLR4 signaling through the attenuation of ubiquitination of TRAF6. Cell Death Dis., 2016, 7, e2313.
[382]
Messingerova, L.; Jonasova, A.; Barancik, M.; Poleková, L.; Šereš, M.; Gibalová, L.; Breier, A.; Sulová, Z. Lenalidomide treatment induced the normalization of marker protein levels in blood plasma of patients with 5q-myelodysplastic syndrome. Gen. Physiol. Biophys., 2015, 34, 399-406.
[383]
Fang, J.; Liu, X.; Bolanos, L.; Barker, B.; Rigolino, C.; Cortelezzi, A.; Oliva, E.N.; Cuzzola, M.; Grimes, H.L.; Fontanillo, C.; Komurov, K.; MacBeth, K.; Starczynowski, D.T. A calcium and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes. Nat. Med., 2016, 22, 727-734.
[384]
Schecter, J.; Galili, N.; Raza, A. MDS: Refining existing therapy through improved biologic insights. Blood Rev., 2012, 26, 73-80.
[385]
Savic, A.; Cemerikic-Martinovic, V.; Dovat, S.; Rajic, N.; Urosevic, I.; Sekulic, B.; Kvrgic, V.; Popovic, S. Angiogenesis and survival in patients with myelodysplastic syndrome. Pathol. Oncol. Res., 2012, 18, 681-690.
[386]
Pardanani, A.; Finke, C.; Lasho, T.L.; Al-Kali, A.; Begna, K.H.; Hanson, C.A.; Tefferi, A. IPSS-independent prognostic value of plasma CXCL10, IL-7 and IL-6 levels in myelodysplastic syndromes. Lekemia, 2012, 26, 693-699.
[387]
Kim, C.K.; Han, D.H.; Ji, Y.S.; Lee, M.S.; Min, C.W.; Park, S.K.; Kim, S.H.; Yun, J.; Kim, H.J.; Kim, K.H.; Lee, K.T.; Won, J.H.; Hong, D.S.; Kim, H.K. Biomarkers of angiogenesis as prognostic factors in myelodysplastic syndrome patients treated with hypomethylating agents. Leuk. Res., 2016, 50, 21-28.
[388]
Invernizzi, R.; Travaglino, E.; Della Porta, M.G. Vascular endothelial growth factor overexpression in myelodysplastic syndrome bone marrow cells: biological and clinical implications. Leuk. Lymphoma, 2017, 58, 1711-1720.
[389]
Dredge, K.; Maarriott, J.B.; Macdonald, C.D.; Man, H.W.; Chen, R.; Muller, G.W.; Stirling, D.; Dalgleish, A.G. Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br. J. Cancer, 2002, 87, 1166-1172.
[390]
Dredge, K.; Horsfall, R.; Robinson, S.P.; Zhang, L.H.; Lu, L.; Tang, Y.; Shirley, M.A.; Muller, G.; Schafer, P.; Stirling, D.; Dalgleish, A.G.; Bartlett, J.B. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc. Res., 2005, 69, 56-63.
[391]
Gandhi, A.K.; Kang, J.; Naziruddin, S.; Parton, A.; Schafer, P.H.; Stirling, D.I. Lenalidomide inhibits proliferation of Namalwa CSN.70 cells and interferes with Gab1 phosphorylation and adaptor protein complex assembly. Leuk. Res., 2006, 30, 849-858.
[392]
Lu, L.; Payvandi, F.; Wu, L.; Zhang, L.H.; Hariri, R.J.; Man, H.W.; Chen, R.S.; Muller, G.W.; Hughes, C.C.; Stirling, D.I.; Schafer, P.H.; Bartlett, J.B. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc. Res., 2009, 77, 78-86.
[393]
Buesche, G.; Dieck, S.; Giagounidis, A.; Göhring, G.; Schlegelberger, B.; Knight, R.; Aul, C.; Kreipe, H. Anti-angiogenic in-vivo effect of lenalidomide and its impact on neoplastic and nonneoplastic hematopoiesis in MDS with del(5q) chromosome abnormality. Blood, 2009, 114, ASH Meeting Abstract 3800.
[394]
Goode, B.; Eck, M.J. Mechanism and function of formins in the control of actin assembly. Annu. Rev. Biochem., 2007, 76, 593-627.
[395]
Aspenström, P. Formin-binding proteins: modulators of formin-dependent actin polymerization. Biochim. Biophys. Acta, 2010, 1803, 174-182.
[396]
Peng, J.; Kitchen, S.M.; West, R.A.; Sigler, R.; Eisenmann, K.M.; Alberts, A.S. Myeloproliferative defects following targeting of the Drf1 gene encoding the mammalian diaphanous related formin mDia1. Cancer Res., 2007, 67, 7565-7571.
[397]
Eisenmann, K.M.; West, R.A.; Hildebrand, K.; Kitchen, S.M.; Peng, J.; Sigler, R.; Zhang, J.; Siminovitch, K.A.; Alberts, A.S. T cell responses in mammalian diaphanous-related formin mDia1 knock.out mice. J. Biol. Chem., 2007, 282, 25152-25158.
[398]
DeWard, A.D.; Leali, K.; West, R.A.; Prendergast, G.C.; Alberts, A.S. Loss of RhoB expression enhances the myelodysplastic phenotype of mammalian diaphanous-related formin mDia1 knockout mice. PLoS One, 2009, 4, e7102.
[399]
Ximeri, M.; Galanopoulos, A.; Klaus, M.; Parcharidou, A.; Giannikou, K.; Psyllaki, M.; Symeonidis, A.; Pappa, V.; Kartasis, Z.; Liapi, D.; Hatzimichael, E.; Kokoris, S.; Korkolopoulou, P.; Sambani, C.; Pontikoglou, C.; Papadaki, H.A. Hellenic MDS Study Group. Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndrome associated with chromosome 5q deletion. Haematologica, 2010, 95, 406-414.
[400]
Sardnal, V.; Rouquette, A.; Kaltenbach, S.; Bally, C.; Chesnais, V.; Leschi, C.; Ades, L.; Santini, V.; Park, S.; Toma, A.; Fenaux, P.; Dreyfus, F.; Fontenay, M.; Kosmider, O.A. G polymorphism in the CRBN gene acts as a biomarker of response to treatment with lenalidomide in low/int-1 risk MDS without del(5q). Leukemia, 2013, 27, 1610-1613.
[401]
Jerez, A.; Gondek, L.P.; Jankowska, A.M.; Makishima, H.; Przychodzen, B.; Tiu, R.V.; O’Keefe, C.L.; Mohamedali, A.M.; Batista, D.; Sekeres, M.A.; McDevitt, M.A.; Mufti, G.J.; Maciejewski, J.P. Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited. J. Clin. Oncol., 2012, 30, 1343-1349.
[402]
Brezinova, J.; Zemanova, Z.; Bystricka, D.; Sarova, I.; Lizcova, L.; Malinova, E.; Izakova, S.; Sajdova, J.; Sponerova, D.; Jonasova, A.; Cermak, J.; Michalova, K. Deletion of the long arm nut not the 5q31 region of chromosome 5 in myeloid malignancies. Leuk. Res., 2012, 36, e43-e45.
[403]
Mallo, M.; del Rey, M.; Ibánez, M.; Calasanz, M.J.; Arenillas, L.; Larráyoz, M.J.; Pedro, C.; Jerez, A.; Maciejewski, J.; Costa, D.; Nomdedeu, M.; Diez-Campelo, M.; Lumbreras, E.; González-Martínez, T.; Marugán, I.; Such, E.; Cervera, J.; Cigudosa, J.C.; Alvarez, S.; Florensa, L.; Hernández, J.M.; Solé, F. Response to lenalidomide in myelodysplastic syndromes with del(5q): influence of cytogenetics and mutations. Br. J. Haematol., 2013, 162, 74-86.
[404]
Zemanova, Z.; Michalova, K.; Buryova, H.; Brezinova, J.; Kostylkova, K.; Bystricka, D.; Novakova, M.; Sarova, I.; Izakova, S.; Lizcova, L.; Ransdorfova, S.; Krejcik, Z.; Merkerova, M.D.; Dohnalova, A.; Siskova, M.; Jonasova, A.; Neuwirtova, R.; Cermak, J. Involvement of deleted chromosome 5 in complex chromosomal aberrations in newly diagnosed myelodysplastic syndromes (MDS) is correlated with extremely adverse prognosis. Leuk. Res., 2014, 38, 537-544.
[405]
Volkert, S.; Kohlmann, A.; Schnittger, S.; Kern, W.; Haferlach, T.; Haferlach, C. Association of the type of 5q loss with complex karyotype, clonal evolution, TP53 mutation status, and prognosis in acute myeloid leukemia and myelodysplastic syndrome. Genes Chromosomes Cancer, 2014, 53, 402-410.
[406]
Schneider, R.K.; Ademà, V.; Heckl, D.; Järås, M.; Mallo, M.; Lord, A.M.; Chu, L.P.; McConkey, M.E.; Kramann, R.; Mullally, A.; Bejar, R.; Solé, F.; Ebert, B.L. Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS. Cancer Cell, 2014, 26, 509-520.
[407]
Woll, P.S.; Kjallquist, U.; Chowdhury, O.; Doolittle, H.; Wedge, D.C.; Thongjuea, S.; Erlandsson, R.; Ngara, M.; Anderson, K.; Deng, Q.; Mead, A.J.; Stenson, L.; Giustacchini, A.; Duarte, S.; Giannoulatou, E.; Taylor, S.; Karimi, M.; Scharenberg, C.; Mortera-Blanco, T.; Macaulay, I.C.; Clark, S.A.; Dybedal, I.; Josefsen, D.; Fenaux, P.; Hokland, P.; Holm, M.S.; Cazzola, M.; Malcovati, L.; Tauro, S.; Bowen, D.; Boultwood, J.; Pellagatti, A.; Pimanda, J.E.; Unnikrishnan, A.; Vyas, P.; Göhring, G.; Schlegelberger, B.; Tobiasson, M.; Kvalheim, G.; Constantinescu, S.N.; Nerlov, C.; Nilsson, L.; Campbell, P.J.; Sandberg, R.; Papaemmanuil, E.; Hellström-Lindberg, E.; Linnarsson, S.; Jacobsen, S.E. Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo. Cancer Cell, 2014, 25, 794-808.
[408]
Heuser, M.; Meggendorfer, M.; Cruz, M.M.A.; Fabisch, J.; Klesse, S.; Köhler, L.; Göhring, G.; Ganster, C.; Shirneshan, K.; Gutermuth, A.; Cerny-Reiterer, S.; Krönke, J.; Panagiota, V.; Haferlach, C.; Koenecke, C.; Platzbecker, U.; Thiede, C.; Schroeder, T.; Kobbe, G.; Ehrlich, S.; Stamer, K.; Döhner, K.; Valent, P.; Schlegelberger, B.; Kroeger, N.; Ganser, A.; Haase, D.; Haferlach, T.; Thol, F. Frequency and prognostic impact of casein kinase 1A1 mutations in MDS patients with deletion of chromosome 5q. Leukemia, 2015, 29, 1942-1945.
[409]
Bello, E.; Pellagatti, A.; Shaw, J.; Mecucci, C.; Kušec, R.; Killick, S.; Giagounidis, A.; Raynaud, S.; Calasanz, M.J.; Fenaux, P.; Boultwood, J. CSNK1A1 mutations and gene expression analysis in myelodysplastic syndromes with del(5q). Br. J. Haematol., 2015, 171, 210-214.
[410]
Saft, L.; Karimi, M.; Ghaderi, M.; Matolcsy, A.; Mufti, G.J.; Kulasekararaj, A.; Göhring, G.; Giagounidis, A.; Selleslag, D.; Muus, P.; Sanz, G.; Mittelman, M.; Bowen, D.; Porwit, A.; Fu, T.; Backstrom, J.; Fenaux, P.; MacBeth, K.J.; Hellström-Lindberg, E. p53 protein expression independently predicts outcome in patients with lower-risk myelodysplastic syndromes with del(5q). Haematologica, 2014, 99, 1041-1049.
[411]
Bally, C.; Renneville, A.; Preudhomme, C.; Legrand, M.; Adès, L.; de Thé, H.; Fenaux, P.; Lehmann-Che, J. Comparison of TP53 mutations screening by functional assay of separated allele in yeast and next-generation sequencing in myelodysplastic syndromes. Leuk. Res., 2015, 39, 1214-1219.
[412]
McGraw, K.L.; Zhang, L.M.; Rollison, D.E.; Basiorka, A.A.; Fulp, W.; Rawal, B.; Jerez, A.; Billingsley, D.L.; Lin, H.Y.; Kurtin, S.E.; Yoder, S.; Zhang, Y.; Guinta, K.; Mallo, M.; Solé, F.; Calasanz, M.J.; Cervera, J.; Such, E.; González, T.; Nevill, T.J.; Haferlach, T.; Smith, A.E.; Kulasekararaj, A.; Mufti, G.; Karsan, A.; Maciejewski, J.P.; Sokol, L.; Epling-Burnette, P.K.; Wei, S.; List, A.F. The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes. Blood Cancer J., 2015, 5, e291.
[413]
Loghavi, S.; Al-Ibrahaemi, A.; Zuo, Z.; Garcia-Manero, G.; Yabe, M.; Wang, S.A.; Kantarjian, H.M.; Yin, C.C.; Miranda, R.N.; Luthra, R.; Medeiros, L.J.; Bueso-Ramos, C.E.; Khoury, J.D. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis. Br. J. Haematol., 2015, 171, 91-99.
[414]
Zhang, L.; McGraw, K.L.; Sallman, D.A.; List, A.F. The role of p53 in myelodysplastic syndromes and acute myeloid leukemia: molecular aspects and clinical implications. Leuk. Lymphoma, 2017, 58, 1777-1790.
[415]
Prebet, T.; Cluzeau, T.; Park, S.; Sekeres, M.A.; Germing, U.; Ades, L.; Platzbecker, U.; Gotze, K.; Vey, N.; Oliva, E.; Sugrue, M.M.; Bally, C.; Kelaidi, C.; Al Ali, N.; Fenaux, P.; Gore, S.D.; Komrokji, R. Outcome of patients treated for myelodysplastic syndromes with 5q deletion after failure of lenalidomide therapy. Oncotarget, 2017, 8, 81926-81935.
[416]
Mallo, M.; Cervera, J.; Schanz, J.; Such, E.; García-Manero, G.; Luño, E.; Steidl, C.; Espinet, B.; Vallespí, T.; Germing, U.; Blum, S.; Ohyashiki, K.; Grau, J.; Pfeilstöcker, M.; Hernández, J.M.; Noesslinger, T.; Giagounidis, A.; Aul, C.; Calasanz, M.J.; Martín, M.L.; Valent, P.; Collado, R.; Haferlach, C.; Fonatsch, C.; Lübbert, M.; Stauder, R.; Hildebrandt, B.; Krieger, O.; Pedro, C.; Arenillas, L.; Sanz, M.Á.; Valencia, A.; Florensa, L.; Sanz, G.F.; Haase, D.; Solé, F. Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q. Leukemia, 2011, 25, 110-120.
[417]
Jonasova, A.; Cermak, J.; Vondrakova, J.; Siskova, M.; Hochova, I.; Kadlckova, E.; Cerna, O.; Sykora, M.; Vozobulova, V.; Seifertova, N.; Michalova, K.; Zemanova, Z.; Brezinova, J.; Belohlavkova, P.; Kostecka, A.; Neuwirtova, R. Thrombocytopenia at diagnosis as an important negative prognostic marker in isolated 5q- MDS (IPSS low and intermediate-1). Leuk. Res., 2012, 36, e222-e224.
[418]
Sugimoto, Y.; Sekeres, M.A.; Makishima, H.; Traina, F.; Visconte, V.; Jankowska, A.; Jerez, A.; Szpurka, H.; O’Keefe, C.L.; Guinta, K.; Afable, M.; Tiu, R.; McGraw, K.L.; List, A.F.; Maciejewski, J. Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del(5q) treated with lenalidomide. J. Hematol. Oncol., 2012, 5, 4.
[419]
Chesnais, V.; Renneville, A.; Toma, A.; Lambert, J.; Passet, M.; Dumont, F.; Chevret, S.; Lejeune, J.; Raimbault, A.; Stamatoullas, A.; Rose, C.; Beyne-Rauzy, O.; Delaunay, J.; Solary, E.; Fenaux, P.; Dreyfus, F.; Preudhomme, C.; Kosmider, O.; Fontenay, M. Groupe Francophone des Myélodysplasies. Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion. Blood, 2016, 127, 749-760.
[420]
Giagounidis, A.A. Where Does Lenalidomide Fit in Non-del(5q) MDS? Curr. Hematol. Malig. Rep., 2015, 10, 303-308.
[421]
Fehninger, T.A.; Byrd, J.C.; Marcucci, G.; Abboud, C.N.; Kefauver, C.; Payton, J.E.; Vij, R.; Blum, W. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood, 2009, 113, 1002-1005.
[422]
Blum, W.; Klisovic, R.B.; Becker, H.; Yang, X.; Rozewski, D.M.; Phelps, M.A.; Garzon, R.; Walker, A.; Chandler, J.C.; Whitman, S.P.; Curfman, J.; Liu, S.; Schaaf, L.; Mickle, J.; Kefauver, C.; Devine, S.M.; Grever, M.R.; Marcucci, G.; Byrd, J.C. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J. Clin. Oncol., 2010, 28, 4919-4925.
[423]
Fehninger, T.A.; Uy, G.L.; Trinkaus, K.; Nelson, A.D.; Demland, J.; Abboud, C.N.; Cashen, A.F.; Stockerl-Goldstein, K.E.; Westervelt, P.; DiPersio, J.F.; Vij, R. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood, 2011, 117, 1828-1833.
[424]
Sekeres, M.A.; Gundacker, H.; Lancet, J.; Advani, A.; Petersdorf, S.; Liesveld, J.; Mulford, D.; Norwood, T.; Willman, C.L.; Appelbaum, F.R.; List, A.F. A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: SWOG Study S0605. Blood, 2011, 118, 523-528.
[425]
Chen, Y.; Kantarjian, H.; Estrov, Z.; Faderl, S.; Ravandi, F.; Rey, K.; Cortes, J.; Borthakur, G. A phase II study of lenalidomide alone in relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndromes with chromosome 5 abnormalities. Clin. Lymphoma Myeloma Leuk., 2012, 12, 341-344.
[426]
Steensma, D.P.; Stone, R.M. Lenalidomide in AML: Del(5q) or who? Blood, 2011, 118, 481-482.
[427]
Ades, L.; Prebet, T.; Stamatoullas, A.; Recher, C.; Guieze, R.; Raffoux, E.; Bouabdallah, K.; Hunault, M.; Wattel, E.; Stalnikiewicz, L.; Toma, A.; Dombret, H.; Vey, N.; Sebert, M.; Gardin, C.; Chaffaut, C.; Chevret, S.; Fenaux, P. Lenalidomide (LEN) combined to intensive chemotherapy (IC) in AML and higher risk MDS with del 5q. Results of a phase II study of the Groupe Francophone des Myelodysplasies. Haematologica, 2017, 102, 728-735.
[428]
DeAngelo, D.J.; Brunner, A.M.; Werner, L.; Avigan, D.; Fathi, A.T.; Sperling, A.S.; Washington, A.; Stroopinsky, D.; Rosenblatt, J.; McMasters, M.; Luptakova, K.; Wadleigh, M.; Steensma, D.P.; Hobbs, G.S.; Attar, E.C.; Amrein, P.C.; Ebert, B.L.; Stone, R.M.; Ballen, K.K. A phase I study of lenalidomide plus chemotherapy with mitoxantrone, etoposide, and cytarabine for the reinduction of patients with acute myeloid leukemia. Am. J. Hematol., 2018, 93, 254-261.
[429]
Higgins, J.J.; Rosen, D.R.; Loveless, J.M.; Clyman, J.C.; Grau, M.J. A gene for nonsyndromic mental retardation maps to chromosome 3p25-pter. Neurology, 2000, 55, 335-340.
[430]
Higgins, J.J.; Pucilowska, J.; Lombardi, R.Q.; Rooney, J.P. A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation. Neurology, 2004, 63, 1927-1931.
[431]
Carling, D. The AMP-activated protein kinase cascade-a unifying system for energy control. Trends Biochem. Sci., 2004, 29, 18-24.
[432]
Lage, R.; Diéguez, C.; Vidal-Puig, A.; López, M. AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol. Med., 2008, 14, 539-549.
[433]
Hardie, D.G.; Ashford, M.L. AMPK: Regulating energy balance at the cellular and whole body levels. Physiology (Bethesda), 2014, 29, 99-107.
[434]
Steinberg, G.R.; Kemp, B.E. AMPK in health and disease. Physiol. Rev., 2009, 89, 1025-1078.
[435]
Lee, K.M.; Jo, S.; Kim, H.; Lee, J.; Park, C.S. Functional modulation of AMP-activated protein kinase by cereblon. Biochim. Biophys. Acta, 2011, 1813, 448-455.
[436]
Lee, K.M.; Yang, S.J.; Kim, Y.D.; Choi, Y.D.; Nam, J.H.; Choi, C.S.; Choi, H.S.; Park, C.S. Disruption of the cereblon gene enhances hepatic AMPK activity and prevents high-fat diet-induced obesity and insulin resistance in mice. Diabetes, 2013, 62, 1855-1864.
[437]
Lee, K.M.; Yang, S.J.; Choi, J.H.; Park, C.S. Functional effects of a pathogenic mutation in Cereblon (CRBN) on the regulation of protein synthesis via the AMPK-mTOR cascade. J. Biol. Chem., 2014, 289, 23343-23352.
[438]
Bavley, C.C.; Rice, R.C.; Fischer, D.K.; Fakira, A.K.; Byrne, M.; Kosovsky, M.; Rizzo, B.K.; Del Prete, D.; Alaedini, A.; Morón, J.A.; Higgins, J.J.; D’Adamio, L.; Rajadhyaksha, A.M. Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual DisabilityCereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase-mTORC1 Translational Pathway. J. Neurosci., 2018, 38, 2780-2795.
[439]
Sawamura, N.; Yamada, M.; Fujiwara, M.; Yamada, H.; Hayashi, H.; Takagi, N.; Asahi, T. The Neuroprotective Effect of Thalidomide against Ischemia through the Cereblon-mediated Repression of AMPK Activity. Sci. Rep., 2018, 8, 2459.
[440]
Gil, M.; Kim, Y.K.; Kim, H.Y.; Pak, H.K.; Park, C.S.; Lee, K.J. Cereblon deficiency confers resistance against polymicrobial sepsis by the activation of AMP activated protein kinase and heme-oxygenase-1. Biochem. Biophys. Res. Commun., 2018, 495, 976-981.
[441]
Koirala, S.; Potts, P.R. An Acetyldegron Triggers CRBN to Take Down the “Q”. Mol. Cell, 2016, 61, 795-796.
[442]
Nguyen, T.V.; Lee, J.E.; Sweredoski, M.; Yang, S.J.; Jeon, S.J.; Harrison, J.S.; Yim, J.H.; Lee, S.G.; Handa, H.; Kuhlman, B.; Jeong, J.S.; Reitsma, J.M.; Park, C.S.; Hess, S.; Deshaies, R.J. Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon. Mol. Cell, 2016, 61, 809-820.
[443]
Ross, C.A.; Poirier, M.A. Protein aggregation and neurodegenerative disease. Nat. Med., 2004, 10, S10-S17.
[444]
Ciechanover, A.; Kwon, Y.T. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp. Mol. Med., 2015, 47, e147.
[445]
Zhou, L.; Hao, Z.; Wang, G.; Xu, G. Cereblon suppresses the formation of pathogenic protein aggregates in a p62-dependent manner. Hum. Mol. Genet., 2018, 27, 667-678.
[446]
Hagner, P.R.; Man, H.W.; Fontanillo, C.; Wang, M.; Couto, S.; Breider, M.; Bjorklund, C.; Havens, C.G.; Lu, G.; Rychak, E.; Raymon, H.; Narla, R.K.; Barnes, L.; Khambatta, G.; Chiu, H.; Kosek, J.; Kang, J.; Amantangelo, M.D.; Waldman, M.; Lopez-Girona, A.; Cai, T.; Pourdehnad, M.; Trotter, M.; Daniel, T.O.; Schafer, P.H.; Klippel, A.; Thakurta, A.; Chopra, R.; Gandhi, A.K. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL. Blood, 2015, 126, 779-789.
[447]
Cubillos-Zapata, C.; Cordoba, R.; Avendaño-Ortiz, J.; Arribas-Jiménez, C.; Hernández-Jiménez, E.; Toledano, V.; Villaescusa, T.; Moreno, V.; López-Collazo, E. CC-122 immunomodulatory effects in refractory patients with diffuse large B-cell lymphoma. OncoImmunology, 2016, 5, e1231290.
[448]
Nakayama, Y.; Kosek, J.; Capone, L.; Hur, E.M.; Schafer, P.H.; Ringheim, G.E. Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity. J. Immunol., 2017, 199, 2388-2407.
[449]
Matyskiela, M.E.; Zhang, W.; Man, H.W.; Muller, G.; Khambatta, G.; Baculi, F.; Hickman, M.; LeBrun, L.; Pagarigan, B.; Carmel, G.; Lu, C.C.; Lu, G.; Riley, M.; Satoh, Y.; Schafer, P. Daniel. T.O.; Carmichael, J.; Cathers, B.E.; Chamberlain, P.P. A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. J. Med. Chem., 2018, 61, 535-542.
[450]
Matyskiela, M.E.; Lu, G.; Ito, T.; Pagarigan, B.; Lu, C.C.; Miller, K.; Fang, W.; Wang, N.Y.; Nguyen, D.; Houston, J.; Carmel, G.; Tran, T.; Riley, M.; Nosaka, L.; Lander, G.C.; Gaidarova, S.; Xu, S.; Ruchelman, A.L.; Handa, H.; Carmichael, J.; Daniel, T.O.; Cathers, B.E.; Lopez-Girona, A.; Chamberlain, P.P. A novel cereblon modulator recruits GSPT1 to the CRL4(CRBN) ubiquitin ligase. Nature, 2016, 535, 252-257.
[451]
Jelinek, T.; Hajek, R. PD-1/PD-L1 inhibitors in multiple myeloma: The present and the future. OncoImmunology, 2016, 5, e1254856.
[452]
Chung, C. Role of Immunotherapy in Targeting the Bone Marrow Microenvironment in Multiple Myeloma: An Evolving Therapeutic Strategy. Pharmacotherapy, 2017, 37, 129-143.
[453]
Gay, F.; D’Agostino, M.; Giaccone, L.; Genuardi, M.; Festuccia, M.; Boccadoro, M.; Bruno, B. Immuno-oncologic approaches: CAR-T cells and checkpoint inhibitors. Clin. Lymphoma Myeloma Leuk., 2017, 17, 471-478.
[454]
Nguyen-Pham, T.N.; Jung, S.H.; Vo, M.C.; Thanh-Tran, H.T.; Lee, Y.K.; Lee, H.J.; Choi, N.R.; Hoang, M.D.; Kim, H.J.; Lee, J.J. Lenalidomide Synergistically Enhances the Effect of Dendritic Cell Vaccination in a Model of Murine Multiple Myeloma. J. Immunother., 2015, 38, 330-339.
[455]
Görgűn, G.; Samur, M.K.; Cowens, K.B.; Paula, S.; Bianchi, G.; Anderson, J.E.; White, R.E.; Singh, A.; Ohguchi, H.; Suzuki, R.; Kikuchi, S.; Harada, T.; Hideshima, T.; Tai, Y.T.; Laubach, J.P.; Raje, N.; Magrangeas, F.; Minvielle, S.; Avet-Loiseau, H.; Munshi, N.C.; Dorfman, D.M.; Richardson, P.G.; Anderson, K.C. Lenalidomide enhances immune checkpoint blockade-induced immune response in multiple myeloma. Clin. Cancer Res., 2015, 21, 4607-4618.
[456]
Tremblay-LeMay, R.; Rastgoo, N.; Chang, H. Modulating PD-L1 expression in multiple myeloma: an alternative strategy to target the PD-1/PD-L1 pathway. J. Hematol. Oncol., 2018, 11, 46.
[457]
Wang, X.; Walter, M.; Urak, R.; Weng, L.; Huynh, C.; Lim, L.; Wong, C.W.; Chang, W.C.; Thomas, S.H.; Sanchez, J.F.; Yang, L.; Brown, C.E.; Pichiorri, F. Htut. M.; Krishnan, A.Y.; Forman, S.J. Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T Cells Against Multiple Myeloma. Clin. Cancer Res., 2018, 24, 106-119.
[458]
Ludwig, H.; Delforge, M.; Facon, T.; Einsele, H.; Gay, F.; Moreau, P.; Avet-Loiseau, H.; Boccadoro, M.; Hajek, R.; Mohty, M.; Cavo, M.; Dimopoulos, M.A.; San-Miguel, J.F.; Terpos, E.; Zweegman, S.; Garderet, L.; Mateos, M.V.; Cook, G.; Leleu, X.; Goldschmidt, H.; Jackson, G.; Kaiser, M.; Weisel, K.; van de Donk, N.W.C.J.; Waage, A.; Beksac, M.; Mellqvist, U.H.; Engelhardt, M.; Caers, J.; Driessen, C.; Sonneveld, P. Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network. Leukemia, 2017.
[http://dx.doi.org/10.1038/leu.2017.353]
[459]
Tan, M.; Fong, R.; Lo, M.; Young, R. Lenalidomide and secondary acute lymphoblastic leukemia: a case series. Hematol. Oncol., 2017, 35, 130-134.
[460]
Ying, L. YinHui, T.; Yunliang, Z.; Sun, H. Lenalidomide and the risk of serious infection in patients with multiple myeloma: a systematic review and meta-analysis. Oncotarget, 2017, 8, 46593-46600.
[461]
Chen, M.; Zhao, Y.; Xu, C.; Wang, X.; Zhang, X.; Mao, B. Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies. Ann. Hematol., 2018, 97(6), 925-944.
[462]
Mauro, F.R.; Foà, R. Gene mutations in lenalidomide-treated CLL. Gene mutations in lenalidomide-treated CLL. Blood, 2018, 131, 1769-1771.
[463]
Takahashi, K.; Hu, B.; Wang, F.; Yan, Y.; Kim, E.; Vitale, C.; Patel, K.P.; Strati, P.; Gumbs, C.; Little, L.; Tippen, S.; Song, X.; Zhang, J.; Jain, N.; Thompson, P.; Garcia-Manero, G.; Kantarjian, H.; Estrov, Z.; Do, K.A.; Keating, M.; Burger, J.A.; Wierda, W.G.; Futreal, P.A.; Ferrajoli, A. Clinical implications of cancer gene mutations in patients with chronic lymphocytic leukemia treated with lenalidomide. Blood, 2018, 131, 1820-1832.
[464]
Ren, Y.; Wang, M.; Couto, S.; Hansel, D.E.; Miller, K.; Lopez-Girona, A.; Bjorklund, C.C.; Gandhi, A.K.; Thakurta, A.; Chopra, R.; Breider, M. A dual color immunohistochemistry assay for measurement of cereblon in multiple myeloma patient samples. Appl. Immunohistochem. Mol. Morphol., 2016, 24, 695-702.
[465]
Blommestein, H.M.; Armstrong, N.; Ryder, S.; Deshpande, S.; Worthy, G.; Noake, C.; Riemsma, R.; Kleijnen, J.; Severens, J.L.; Al, M.J. Lenalidomide for the treatnent of low- or intermediate-1-risk myelodysplastic syndromes associated with deletion 5q cytogenetic abnormality: an evidence review of the NICE submission from Celgene. Pharmacoeconomics, 2016, 34, 23-31.
[466]
Rajkumar, S.V.; Harousseau, J.L. Next-generation multiple myeloma treatment: a pharmacoeconomic perspective. Blood, 2016, 128, 2757-2764.
[467]
Santini, V.; Almeida, A.; Giagounidis, A.; Platzbecker, U.; Buckstein, R.; Beach, C.L.; Guo, S.; Altincatal, A.; Wu, C.; Fenaux, P. The effect of lenalidomide on health-related quality of life in patients with lower-risk non-del(5q) myelodysplastic syndromes: results from the MDS-005 study. Clin. Lymphoma Myeloma Leuk., 2018, 18, 136-144.
[468]
Almeida, A.; Fenaux, P.; Garcia-Manero, G.; Goldberg, S.L.; Gröpper, S.; Jonasova, A.; Vey, N.; Castaneda, C.; Zhong, J.; Beach, C.L.; Santini, V. Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial. Leuk. Lymphoma, 2018, doi: 10.1080/10428194. 2017.1421758. [Epub ahead of print]


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 19
ISSUE: 1
Year: 2019
Page: [51 - 78]
Pages: 28
DOI: 10.2174/1871529X18666180522073855
Price: $58

Article Metrics

PDF: 52
HTML: 6
EPUB: 1