Lack of Association of Multidrug Resistance Gene-۱ Polymorphisms with Treatment Outcome in Chronic Myeloid Leukemia Patients Treated with Imatinib

Background: Despite the impressive results obtained with imatinib, inadequate response or resistance are observed in certain patients. It is known that imatinib is a substrate of a multidrug resistance gene (MDR۱). Thus, interindividual genetic differences linked to single nucleotide polymorphisms in MDR۱ may influence the metabolism of imatinib. The present study has aimed to examine the impact of MDR۱ polymorphisms on the hematologic and cytogenetic responses in ۷۰ chronic myeloid leukemia patients who received imatinib.Methods: We used a polymerase chain reaction followed by restriction fragment length polymorphism to identify different profiles of ۱۲۳۶C>T, ۲۶۷۷G>T and ۳۴۳۵C>T in MDR۱.Results: The distribution of the three SNPs in responders and poor responders did not show any particular trend (P>۰.۰۵). The T allele was slightly higher in responders, but not significantly regardless of the type of SNP (۴۰.۳% vs. ۳۳.۸% for ۱۲۳۶C>T; ۲۵% vs. ۱۴.۷% for ۲۶۷۷G>T and ۳۳.۳% vs. ۲۲% for ۳۴۳۵C>T). The dominant model showed a similar trend (P>۰.۰۵). Diplotypes composed by the T allele in different exons were frequent in responders. Haplotype analysis showed that ۱۲۳۶C-۲۶۷۷G-۳۴۳۵C was slightly higher in poor responders (۶۰.۰۲%) compared to responders (۵۰.۴۲%). However, ۱۲۳۶T-۲۶۷۷T-۳۴۳۵T was frequent in responders (۱۶.۹۸%) compared to poor responders (۱۳.۱%). Overall, none of the haplotypes were associated with IM response in our cohort (global haplotype association test, P=۰.۳۹).Conclusion: The identification of ۱۲۳۶C>T, ۲۶۷۷G>T and ۳۴۳۵C>T polymorphisms may not be advantageous to predict imatinib response for our chronic myeloid leukemia patients.