Impact Of Drug Transporters Abcb1 And Abcg2 And Regulators Of Xenobiotic Transport And Metabolism Pxr And Car Gene Polymorphisms On Clinical Efficacy Of Imatinib In Chronic Myeloid Leukemia (Cml)

Background: Inherited background in mechanisms regulating cellular uptake, elimination and metabolism of imatinib and other BCR-ABL tyrosine kinase inhibitors may influence treatment outcome in chronic myeloid leukemia (CML). Despite good efficacy of imatinib in CML therapy, a proportion of patients show suboptimal responses or even primary resistance. Imatinib is a well-established substrate of ABC-superfamily xenobiotic transporters ABCB1 (MDR1, Pg-P) and ABCG2 (BCRP). However, the results of published studies regarding impact of ABCB1 and ABCG2 single nucleotide polymorphisms (SNPs) on imatinib treatment outcome have shown discrepant results. Moreover, little is known on the potential role of polymorphisms of regulators of xenobiotic transport and metabolism, pregnane X receptor (PXR, NR1|2) and constitutive androstane receptor (CAR, NR1|3) in imatinib efficacy.