Document Type: Original Article

Authors

1 Genetics and Molecular Pathology Laboratory, Medical School of Casablanca, Hassan II University, Casablanca, Morocco

2 Department of Onco-Hematology, Ibn Rochd University Hospital, Casablanca, Morocco

Abstract

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 (MDR1). Thus, interindividual genetic differences linked to single nucleotide polymorphisms in MDR1 may influence the metabolism of imatinib. The present study has aimed to examine the impact of MDR1 polymorphisms on the hematologic and cytogenetic responses in 70 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 1236C>T, 2677G>T and 3435C>T in MDR1.Results: The distribution of the three SNPs in responders and poor responders did not show any particular trend (P>0.05). The T allele was slightly higher in responders, but not significantly regardless of the type of SNP (40.3% vs. 33.8% for 1236C>T; 25% vs. 14.7% for 2677G>T and 33.3% vs. 22% for 3435C>T). The dominant model showed a similar trend (P>0.05). Diplotypes composed by the T allele in different exons were frequent in responders. Haplotype analysis showed that 1236C-2677G-3435C was slightly higher in poor responders (60.02%) compared to responders (50.42%). However, 1236T-2677T-3435T was frequent in responders (16.98%) compared to poor responders (13.1%). Overall, none of the haplotypes were associated with IM response in our cohort (global haplotype association test, P=0.39).Conclusion: The identification of 1236C>T, 2677G>T and 3435C>T polymorphisms may not be advantageous to predict imatinib response for our chronic myeloid leukemia patients.