Influence of ABCB1 C3435T and ABCG2 C421A Gene Polymorphisms in Response to Imatinib Mesylate in Chronic Myeloid Leukemia Patients

Despite the excellent efficacy results of IM treatment in CML patients, resistance to IM has emerged as a significant problem. Genetic variations in genes involved in drug transportation encoding membrane transporters such as ABCB1 and ABCG2 might influence the pharmacokinetic and metabolism of IM. The genotype of a patient is increasingly recognized in influencing the response to the treatment. In this study, the relationship between IM response and 2 SNPs (ABCB1 C3435T and ABCG2 C421A) were investigated among Malaysian CML patients undergoing IM treatment. Peripheral blood was withdrawn from 91 healthy individuals and 45 CML patients undergoing IM treatment. DNA was extracted from the blood samples and followed by the genotyping technique using PCR-RFLP method. The results showed the homozygous wild type genotype (CC) of SNP ABCB1 C3435T was higher in CML patients showing IM resistant compared to IM good response CML patients with p = 0.004. Interestingly, IM resistance was lower for patients homozygous for the A allele of ABCG2 SNP C421A compared to patients with C allele (33% vs. 64%, p=0.0001). Besides, these 2 SNPs were found not to contribute to the genetic susceptibility of CML when evaluated with healthy control subjects. These preliminary results prompt us to suggest the possibility of exploring these SNPs as biomarkers to predict the response to IM in CML patients prior to IM treatment. Index Terms—ABCB1 C3435T, ABCG2 C421A, polymorphisms, imatinib mesylate, chronic myeloid leukemia (CML)