Lack of Association of Multidrug Resistance Gene-1 Polymorphisms with Treatment Outcome in Chronic Myeloid Leukemia Patients Treated with Imatinib

Background: despite the impressive results obtained with imatinib, inadequateresponse or resistance are observed in certain patients. it is known that imatinib is asubstrate of a multidrug resistance gene (mdr1). thus, interindividual geneticdifferences linked to single nucleotide polymorphisms in mdr1 may influence themetabolism of imatinib. the present study has aimed to examine the impact of mdr1polymorphisms on the hematologic and cytogenetic responses in 70 chronic myeloidleukemia patients who received imatinib.methods: we used a polymerase chain reaction followed by restriction fragmentlength polymorphism to identify different profiles of 1236c > t, 2677g > t and 3435c > tin mdr1.results: the distribution of the three snps in responders and poor responders didnot 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 modelshowed a similar trend (p > 0.05). diplotypes composed by the t allele in different exonswere frequent in responders. haplotype analysis showed that 1236c-2677g-3435c wasslightly higher in poor responders (60.02%) compared to responders (50.42%).however, 1236t-2677t-3435t was frequent in responders (16.98%) compared topoor responders (13.1%). overall, none of the haplotypes were associated with imresponse in our cohort (global haplotype association test, p=0.39).conclusion: the identification of 1236c > t, 2677g > t and 3435c > t polymorphismsmay not be advantageous to predict imatinib response for our chronic myeloid leukemiapatients.