Multidrug Resistance Gene (MDR1) C3435T Polymorphism and Imatinib Response in Patients with Chronic Myeloid Leukemia

• Published in: Blood 2011-11, Vol.118 (21), p.1692-1692
• Main Authors: Eskazan, Ahmet Emre, Tatonyan, Suzin Catal, Salihoglu, Ayse, Gulturk, Emine, Ar, M. Cem, Aydin, Seniz Ongoren, Baslar, Zafer, Ferhanoglu, A. Burhan, Tuzuner, Nukhet, Aydin, Yildiz, Ozbek, Ugur, Soysal, Teoman
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.1692.1692

Abstract 1692 There has been a remarkable improvement in the management of chronic myeloid leukemia (CML) after imatinib mesylate (IM) became available in the market, but there is still a group of patients who are resistant to imatinib. Although point mutations in the BCR-ABL kinase domain is the most common mechanism for resistance in patients with CML receiving tyrosine kinase inhibitor (TKI) therapy, there are several mechanisms that can play a role in the resistance to TKIs. Multi drug resistance gene (MDR1) [ABCB1 (ATP-binding cassette, sub-family B (MDR/TAP), member 1) ] product is an ATP-driven efflux pump contributing to the pharmacokinetics of drugs that are P-glycoprotein (P-gp) substrates and to the multidrug resistance of cancer cells. More than 50 single nucleotide polymorphisms (SNPs) have been identified concerning the MDR1 gene, and SNP polymorphisms may affect the expression and function of the P-gp. The SNPs T1236C, G2677T/A, and C3435T are the most common variants in the coding region of ABCB1. Imatinib is a substrate of P-gp-mediated efflux, and P-gp mediated drug efflux can play a role in IM resistance. So identifying these SNPs may allow to predict the drug disposition and responses to IM in CML patients. The aim of the study was to identify the C3435T SNP variants, and the associations between MDR1 C3435T polymorphism and IM efficacy in our CML patients. Between December 2010 and March 2011, 110 chronic phase (CP) CML patients who consecutively visited our outpatient clinic were enrolled in this study. Hematologic, cytogenetic and molecular response patterns to IM as well as the association between MDR1 C3435T polymorphism and responses to imatinib were evaluated in our patient cohort. MDR1 C3435T polymorphisms were detected by real-time polymerase chain reaction (RT-PCR). We could assess complete cytogenetic response (CCyR) and major molecular response (MMR) in one hundred and six patients (96%) among these 110 patients. The differences in genotype frequencies in all patients taking imatinib treatment was determined by using the chi-square test. All tests were two-sided, and p