ABCB1 POLYMORPHISMS AND IMATINIB RESPONSE IN TUNISIAN PATIENTS WITH CHRONIC MYELOID LEUKEMIA.

Introduction: The success of imatinib mesylate has become a paradigm shift in chronic myeloid leukemia (CML) treatment. However, despite its high efficiency, resistance to imatinib has emerged as a significant problem, which may in part be caused by pharmacogenetic variability. Genetic variations of ABCB1 gene, an efflux pump transporter, may affect intracellular drug import. In this study, we aimed to examine whether the 3 most relevant polymorphisms (C1236T, G2677T/A, C3435T) may influence response to imatinib. Materials and Methods: Sixty nine CML Tunisian patients, undergoing imatinib therapy, were included in this study. According to European leukemia guidelines, 35 patients were responders to imatinib and 34 patients were resistant. ABCB1 polymorphisms were genotyped using polymerase chain reaction followed by direct sequencing approach. Pairwise linkage desequiliribium tests and haplotypes analysis were also assessed in CML patients. Results: our results showed that the optimal response rate to imatinib did not differ significantly between C1236T or C3435T genotypes. However, heterozygous variant G2677A was fond only in 4 imatinib non-responders' patients, the remainder harbored the GG, GT and TT genotypes. This results is statistically insignificant due to the small number of patients with this form of A allele. In addition, haplotype analysis showed that the 1236C-2677A-3435C haplotype was observed only in imatinib non-responders' patients suggesting that CAC haplotype was linked to higher risk of imatinib resistance. Conclusion: analyses of ABCB1 haplotypes should be taken into account to study the relationship between ABCB1 genotypes and imatinib efficacy in CML Tunisian patients. [ABSTRACT FROM AUTHOR]