Influence of multi-drug transporter gene ABCG2 polymorphism (C421A) in clinical out care in some Iraqi chronic myeloid leukemia patients treated with imatinib mesylate

Abstract

In CML patients, Imatinib Mesylate (IM) treatment is a good choice with an excellent efficacy outcome. But unfortunately, a significant obstacle of IM resistance has emerged relating to the genetic polymorphism in drug transporter genes such as ABCG2 which effects the metabolism and pharmacokinetic IM. This study investigate the influence of ABCG2 C421A SNP in IM response among some Iraqi CML Patients (71 patients : 43 Male , 28 Female) aged between ( 20-70 ) years in chronic phase with positive Philadelphia (Ph) chromosome, including 11 newly diagnosed , and 60 treated with standard dose IM (400mg) on frontline treatment , 30 of them  were IM response  and 30 resistance to IM drug , on the other hand  25 apparently healthy individuals were included as control group. After the patients were informed about the details of the research, they were approved to take samples of their blood for study , 3ml of peripheral blood was withdrawn  from CML patients and  control groups  . The frequency of homozygous mutant  genotype (AA) of SNPabcg2 C421Awas significant higher in IM resistant CML patients as compared to IM good response CML patients with (O.R=1.309 and p < 0.01) . The SNP abcg2 C421A was found to contribute to the genetic susceptibility of CML when evaluated with healthy control subjects. These reconnoitering results give a reasonable cause to explore such SNPs to be used as a biomarker in prediction the response to IM treatment before getting started.