Generic placeholder image

Clinical Cancer Drugs


ISSN (Print): 2212-697X
ISSN (Online): 2212-6988

Research Article

The Association Between the Level of Leukemic Stem Cells and Treatment Response Among Chronic Myeloid Leukemia Patients Treated with Imatinib Mesylate

Author(s): Shinta Oktya Wardhani*, Hani Susianti, Puji Rahayu and Yuyun Yueniwati

Volume 7, Issue 2, 2020

Page: [119 - 124] Pages: 6

DOI: 10.2174/2212697X07999200824115628

open access plus


Background: The failure of imatinib therapy in patients with chronic myeloid leukemia (CML) is associated with the presence of leukemic stem cell (LSC), and the altered LSC level was reported to occur earlier in the progression of CML.

Objective: The study aimed to assess the association between the level of LSC and treatment response among CML patients treated with imatinib mesylate.

Methods: A cross-sectional study was conducted in Saiful Anwar Hospital. All participants were divided into two groups, response and non-response group. To assess the level of LSC, flow cytometry was conducted conforming with BD Bioscience. The association and effect estimates were determined using multiple logistic regression.

Results and Discussion: A total of 29 response and non-response CML patients treated with imatinib therapy were recruited for our study. After six months of imatinib therapy, we found that elevated levels of leukocytes, thrombocytes, basophils, and blast cells were associated with treatment failure among CML patients treated with imatinib. Moreover, we also found that the LSC level was observed significantly higher in the non-response group compared to the response group among CML patients treated with imatinib.

Conclusion: Our study reveals that the elevated level of LSC is considered as an important factor to predict the failure of imatinib therapy among CML patients.

Keywords: Imatinib mesylate, treatment response, chronic myeloid leukemia, stem cells, imatinib therapy, leukocytes.

Graphical Abstract
Flis S, Chojnacki T. Chronic myelogenous leukemia, a still unsolved problem: pitfalls and new therapeutic possibilities. Drug Des Devel Ther 2019; 13: 825-43.
[] [PMID: 30880916]
Höglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol 2015; 94(Suppl. 2): S241-7.
[] [PMID: 25814090]
Granatowicz A, Piatek CI, Moschiano E, El-Hemaidi I, Armitage JD, Akhtari M. An Overview and Update of Chronic Myeloid Leukemia for Primary Care Physicians. Korean J Fam Med 2015; 36(5): 197-202.
[] [PMID: 26435808]
Valent P. Imatinib-resistant chronic myeloid leukemia (CML): Current concepts on pathogenesis and new emerging pharmacologic approaches. Biologics 2007; 1(4): 433-48.
[PMID: 19707313]
Srivastava S, Dutt S. Imatinib mesylate resistance and mutations: An Indian experience. Indian J Med Paediatr Oncol 2013; 34(3): 213-20.
[] [PMID: 24516315]
Milojkovic D, Nicholson E, Apperley JF, et al. Early prediction of success or failure of treatment with second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia. Haematologica 2010; 95(2): 224-31.
[] [PMID: 19833633]
Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull 2017; 7(3): 339-48.
[] [PMID: 29071215]
Muhammad N, Bhattacharya S, Steele R, Phillips N, Ray RB. Involvement of c-Fos in the Promotion of Cancer Stem-like Cell Properties in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2017; 23(12): 3120-8.
[] [PMID: 27965308]
Bhatia R. Targeting Leukemia Stem Cell Resistance in Chronic Myelogenous Leukemia. Trans Am Clin Climatol Assoc 2019; 130: 246-54.
[PMID: 31516189]
Zhao Y, Wu K, Wu Y, et al. Characterization of Imatinib Resistant CML Leukemic Stem/Initiating Cells and Their Sensitivity to CBP/Catenin Antagonists. Curr Mol Pharmacol 2018; 11(2): 113-21.
[] [PMID: 28933312]
Zhao W, Li Y, Zhang X. Stemness-Related Markers in Cancer. Cancer Transl Med 2017; 3(3): 87-95.
[] [PMID: 29276782]
Visvader JE, Lindeman GJ. Cancer stem cells: current status and evolving complexities. Cell Stem Cell 2012; 10(6): 717-28.
[] [PMID: 22704512]
Bixby D, Talpaz M. Seeking the causes and solutions to imatinib-resistance in chronic myeloid leukemia. Leukemia 2011; 25(1): 7-22.
[] [PMID: 21102425]
Mustjoki S, Richter J, Barbany G, et al. Nordic CML Study Group (NCMLSG). Impact of malignant stem cell burden on therapy outcome in newly diagnosed chronic myeloid leukemia patients. Leukemia 2013; 27(7): 1520-6.
[] [PMID: 23328954]
Thielen N, Richter J, Baldauf M, et al. Leukemic Stem Cell Quantification in Newly Diagnosed Patients With Chronic Myeloid Leukemia Predicts Response to Nilotinib Therapy. Clin Cancer Res 2016; 22(16): 4030-8.
[] [PMID: 27006491]
Kantarjian HM, Giles FJ, Bhalla KN, et al. Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood 2011; 117(4): 1141-5.
[] [PMID: 21098399]
Chu S, McDonald T, Lin A, et al. Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment. Blood 2011; 118(20): 5565-72.
[] [PMID: 21931114]
Hoffmann VS, Baccarani M, Hasford J, et al. The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries. Leukemia 2015; 29(6): 1336-43.
[] [PMID: 25783795]
Assouline S, Lipton JH. Monitoring response and resistance to treatment in chronic myeloid leukemia. Curr Oncol 2011; 18(2): e71-83.
[] [PMID: 21505592]
Culen M, Borsky M, Nemethova V, et al. Quantitative assessment of the CD26+ leukemic stem cell compartment in chronic myeloid leukemia: patient-subgroups, prognostic impact, and technical aspects. Oncotarget 2016; 7(22): 33016-24.
[] [PMID: 27145281]
Qin YZ, Jiang Q, Jiang H, et al. Combination of White Blood Cell Count at Presentation With Molecular Response at 3 Months Better Predicts Deep Molecular Responses to Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients. Medicine (Baltimore) 2016; 95(2)e2486
[] [PMID: 26765457]
Houshmand M, Simonetti G, Circosta P, et al. Chronic myeloid leukemia stem cells. Leukemia 2019; 33(7): 1543-56.
[] [PMID: 31127148]
Cortes J, Quintás-Cardama A, Kantarjian HM. Monitoring molecular response in chronic myeloid leukemia. Cancer 2011; 117(6): 1113-22.
[] [PMID: 20960522]
El-Ghammaz AM, Hamed GM, Fattah MFA, Attia MH. Basophil progenitor marker histamine and its relation to the treatment response in Egyptian chronic myeloid leukemia patients. Egyptian Journal of Haematology 2015; 40: 30.
Valent P, Horny HP, Arock M. The underestimated role of basophils in Ph+ chronic myeloid leukaemia. Eur J Clin Invest 2018; 48(10)e13000
[] [PMID: 30019447]
Bocchia M, Sicuranza A, Abruzzese E, et al. Residual Peripheral Blood CD26+ Leukemic Stem Cells in Chronic Myeloid Leukemia Patients During TKI Therapy and During Treatment-Free Remission. Front Oncol 2018; 8: 194.
[] [PMID: 29900128]
Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest 2011; 121(1): 396-409.
[] [PMID: 21157039]
Kabat GC, Wu JW, Moore SC, et al. Lifestyle and dietary factors in relation to risk of chronic myeloid leukemia in the NIH-AARP Diet and Health Study. Cancer Epidemiol Biomarkers Prev 2013; 22(5): 848-54.
[] [PMID: 23625904]

© 2022 Bentham Science Publishers | Privacy Policy