Effects of GSTP1 Ile105Val polymorphism on both susceptibility and treatment response of chronic myeloid leukemia

Abstract

Chronic myeloid leukemia (CML) is a multifactorial disease, which is caused by a complicated interaction between genetic and environmental agents. The Gluthation- S-transferase (GST) covers a family of multifunctional enzymes that involved in the detoxification of various toxic substances and anticancer drugs. Some polymorphisms in GSTs gene, could influence cancer susceptibility and drug resistance. The aim of the present study was to explore the influence of GSTP1 105 Ile/Val (rs1695) gene polymorphism on both CML susceptibility and response to Imatinib.DNA was extracted from blood samples by salting-out method; the Ile105Val polymorphism was genotyped in all participants (200 controls and 112 patients with chronic myeloid leukemia) by using PCR-RFLP method.The results of the present study revealed the absence of a significant association between GSTP1 105 Ile/Val gene polymorphism and CML risk, the variant allele Val was more frequent among controls (32%) than among patients (30)%). However, Hematologic response loss, cytogenetic resistance, side effects related to imatinib and none cytogenetic responders were more frequent among patients harboring val/val genotype compared with patients carrying Ile/ Ile and Ile/val genotypes.We have shown that this polymorphism is not associated with the risk of CML, but it influences the response of our patients treated by imatinib.