Generic placeholder image

Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Research Article

Mutation Analysis of ABL1 Gene and its Relation to the Achievement of Major Molecular Response in Indonesian Chronic Myeloid Leukemia Patients

Author(s): Reni Widyastuti, Melva Louisa, Ikhwan Rinaldi*, Riki Nova , Instiaty Instiaty and Rizky Priambodo

Volume 17, Issue 1, 2020

Page: [48 - 54] Pages: 7

DOI: 10.2174/1875692117666190925115852

open access plus

Abstract

Background: Imatinib mesylate is the first tyrosine kinase inhibitor approved for chronic myeloid leukemia (CML) therapy. Imatinib is an effective drug. However, previous studies have shown that about 20-30% of patients eventually would develop resistance to imatinib. Approximately 40% of imatinib resistance is associated with BCRABL kinase domain mutation. One of the most common and serious variations account for imatinib response is T315I of ABL1 gene.

Objective: The study aimed to examine the association of T315I mutation with the ABL1 gene and its relation to major molecular response (MMR) achievement in CML patients. This study also examined other mutations adjacent to T315I, i.e., F311I, F317L, and different possible variations in the ABL1 gene.

Methods: This was a cross-sectional study on Indonesian CML patients in chronic phase. We analyzed 120 blood samples from patients in chronic phase who have received imatinib mesylate (IM) for ≥12 months.

Results: There were no T315I, F311I, and F317L mutations found in this study. However, we found another variation, which was 36 substitutions from A to G at position 163816 of ABL1 gene (according to NG_012034.1).

Conclusion: We found no T315I, F311I, and F317L mutations in this study. Our findings suggest that there might be other factors that influenced the MMR achievement in our study patients. However, there were 36 substitutions from A to G at position 163.816 (according to NG_012034.1) that needed further examination to explore the significance of this mutation in clinical practice.

Keywords: Imatinib, BCR-ABL, T315I, chronic myeloid leukemia, F311I, F317L.

Graphical Abstract
[1]
Apperley JF. Chronic myeloid leukaemia. Lancet 2015; 385(9976): 1447-59.
[http://dx.doi.org/10.1016/S0140-6736(13)62120-0] [PMID: 25484026]
[2]
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol 2018; 93(3): 442-59.
[http://dx.doi.org/10.1002/ajh.25011] [PMID: 29411417]
[3]
Höglund M, Sandin F, Simonsson B. Epidemiology of chronic myeloid leukaemia: an update. Ann Hematol 2015; 94(Suppl. 2): S241-7.
[http://dx.doi.org/10.1007/s00277-015-2314-2] [PMID: 25814090]
[4]
Au WY, Caguioa PB, Chuah C, et al. Chronic myeloid leukemia in Asia. Int J Hematol 2009; 89(1): 14-23.
[http://dx.doi.org/10.1007/s12185-008-0230-0] [PMID: 19101781]
[5]
Rajabto W, Harryanto A, Tadjoedin H, Harimurti K. Hubungan gambaran klinis dan laboratorium hematologis antara leukemia granulositik kronik Ph(+)/BCR-ABL (+) dengan bentuk kelainan Ph/BCR-ABL lainnya. J penyakit dalam Indones 2018; 5: 11-5.
[http://dx.doi.org/10.7454/jpdi.v5i1.167]
[6]
Milojkovic D, Apperley J. Mechanisms of resistance to imatinib and second-generation tyrosine inhibitors in chronic myeloid leukemia. Clin Cancer Res 2009; 15(24): 7519-27.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1068] [PMID: 20008852]
[7]
Yamamoto M, Kurosu T, Kakihana K, Mizuchi D, Miura O. The two major imatinib resistance mutations E255K and T315I enhance the activity of BCR/ABL fusion kinase. Biochem Biophys Res Commun 2004; 319(4): 1272-5.
[http://dx.doi.org/10.1016/j.bbrc.2004.05.113] [PMID: 15194504]
[8]
Gibbons DL, Pricl S, Kantarjian H, Cortes J, Quintás-Cardama A. The rise and fall of gatekeeper mutations? The BCR-ABL1 T315I paradigm. Cancer 2012; 118(2): 293-9.
[http://dx.doi.org/10.1002/cncr.26225] [PMID: 21732333]
[9]
Saussele S, Hehlmann R, Fabarius A, et al. Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV. Leukemia 2018; 32(5): 1222-8.
[http://dx.doi.org/10.1038/s41375-018-0055-7] [PMID: 29479070]
[10]
Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013; 122(6): 872-84.
[http://dx.doi.org/10.1182/blood-2013-05-501569] [PMID: 23803709]
[11]
Press RD. Major molecular response in CML patients treated with tyrosine kinase inhibitors: the paradigm for monitoring targeted cancer therapy. Oncologist 2010; 15(7): 744-9.
[http://dx.doi.org/10.1634/theoncologist.2010-0055] [PMID: 20566700]
[12]
Reddy EP, Aggarwal AK. The ins and outs of bcr-abl inhibition. Genes Cancer 2012; 3(5-6): 447-54.
[http://dx.doi.org/10.1177/1947601912462126] [PMID: 23226582]
[13]
Poláková KM, Lopotová T, Klamová H, Moravcová J. High-resolution melt curve analysis: initial screening for mutations in BCR-ABL kinase domain. Leuk Res 2008; 32(8): 1236-43.
[http://dx.doi.org/10.1016/j.leukres.2008.01.010] [PMID: 18308387]
[14]
Rejali L, Poopak B, Hasanzad M, et al. Characterizing of four common BCR-ABL kinase domain mutations (T315I, Y253H, M351T and E255K) in Iranian chronic myelogenous leukemia patients with imatinib resistance. Iran J Cancer Prev 2015; 8(3) e2334
[http://dx.doi.org/10.17795/ijcp2334] [PMID: 26413254]
[15]
Chahardouli B, Zaker F, Mousavi SA, et al. Evaluation of T315I mutation frequency in chronic myeloid leukemia patients after imatinib resistance. Hematology 2013; 18(3): 158-62.
[http://dx.doi.org/10.1179/1607845412Y.0000000050] [PMID: 23540562]
[16]
Dhahi MA, Matti BF, Fadel S. Molecular screening for T315I and F317L resistance mutations in Iraqi chronic myeloid leukemia non-responders patients to imatinib. Cancer Clin Oncol 2013; 2(2): 55-8.
[http://dx.doi.org/10.5539/cco.v2n2p55]
[17]
Mat Yusoff Y, Abu Seman Z, Othman N, et al. Prevalence of BCR-ABL T315I mutation in Malaysian patients with imatinib-resistant chronic myeloid leukemia. Asian Pac J Cancer Prev 2018; 19(12): 3317-20.
[http://dx.doi.org/10.31557/APJCP.2018.19.12.3317] [PMID: 30583336]
[18]
Kim H, Kim SH, Kim HJ, et al. Comparison of frequency and sensitivity of BCR-ABL1 kinase domain mutations in asian and white patients with imatinib-resistant chronic-phase chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk 2018; 18(10): e391-9.
[http://dx.doi.org/10.1016/j.clml.2018.06.031]
[19]
Cortes J, Quintás-Cardama A, Kantarjian HM. Monitoring molecular response in chronic myeloid leukemia. Cancer 2011; 117(6): 1113-22.
[http://dx.doi.org/10.1002/cncr.25527] [PMID: 20960522]
[20]
Haznedaroglu IC. Monitoring the response to tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML). Mediterr J Hematol Infect Dis 2014; 6(1) e2014009
[http://dx.doi.org/10.4084/mjhid.2014.009] [PMID: 24455118]
[21]
Casetti L. New roles of STAT5 factors in chronic myeloid leukemia cell maintenance. Paris: Université René Descartes 2013.
[22]
Gambacorti-Passerini C, Barni R, le Coutre P, et al. Role of alpha1 acid glycoprotein in the in vivo resistance of human BCR-ABL(+) leukemic cells to the abl inhibitor STI571. J Natl Cancer Inst 2000; 92(20): 1641-50.
[http://dx.doi.org/10.1093/jnci/92.20.1641] [PMID: 11036109]
[23]
Mahon FX, Belloc F, Lagarde V, et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood 2003; 101(6): 2368-73.
[http://dx.doi.org/10.1182/blood.V101.6.2368] [PMID: 12609962]
[24]
Crossman LC, Druker BJ, Deininger MW, Pirmohamed M, Wang L, Clark RE. hOCT 1 and resistance to imatinib. Blood 2005; 106(3): 1133-4.
[http://dx.doi.org/10.1182/blood-2005-02-0694] [PMID: 16033955]

© 2024 Bentham Science Publishers | Privacy Policy