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

Abstract

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 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, associations between IM response and 2 SNPs in genes involved in IM pharmacokinetics (ABCB1 C3435T, ABCG2 C421A) were investigated among 45 Malaysian CML patients undergoing IM treatment. The results showed the wild type CC genotypes were higher in CML patients showing IM resistant compared to IM good response CML patients with p = 0.004. Resistance was lower for patients homozygous for the A allele of C421A compared to patients with C allele (33% vs. 64%, p=0.0001). 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.