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Association of MDR1 gene polymorphism (G2677T) with chronic myeloid leukemia

Kagita Sailaja, Damineni Surekha, Dunna Nageswara Rao, Digimarti Raghunadharao, Satti Vishnupriya

Imatinib mesylate is the most opted drug used for treating ph+ve chronic myeloid leukemia (CML) patients. The up-regulation of drug transporters (ABCB1-ABCG2) is one of specific causes of Imatinib resistance. Imatinib (IM) is a substrate of the P-glycoprotein pump, which is encoded by MDR1/ABCB1 gene. Our main objective is to investigate the influence of MDR1 gene polymorphisms in CML patients. A total of 262 CML and 252 control samples were analysed for MDR1 gene (G2677T) polymorphism using PCR- RFLP technique. Genotype distribution revealed slight elevation of TT genotype frequency in CML patients (42.7%) compared to controls (38.5%). Patients in advanced phase had higher TT genotype frequency compared to patients in early phases. The frequency of heterozygous GT genotype was found to be increased in hematological poor responders (52.4%) compared to major responders (32.4%) and minor responders (30.0%). Interestingly, the frequencies of GG and GT genotypes were increased in cytogenetic poor responders with corresponding increase in G allele frequency (0.54) as compared to major responders (0.34). These results suggest that the 2677G allele with increased efflux of IM might be responsible for poor response in CML patients.