Study of the Possible Correlation between MRP1 Gene Polymorphisms (C2217T, G2168A, T825C, G816A, G1299, G-260C, A-275G, G2268A) and its mRNA Expression in Acute Leukemic Patients with MDR Phenotype

Many cancer cells during the chemotherapy procedure become resistance to several drugs the phenomenon which is called multidrug resistance (MDR). One of the important mechanisms responsible for MDR is the over expression of ABC transporter genes. One of the most extensively studied genes involved in MDR is multidrug resistance protein 1 (MRP1). Over expression of this gene has been detected in many cell lines and cancer cells with MDR phenotype. Two known mechanism inducing over expression of this gene is gene amplification and the presence of SNPs. We have shown that the over expression of this gene is associated with the MDR in Iranian leukemic patients. However, MRP1 gene amplification could not be identified in any of those patients. We aimed to investigate the possible association between the expression level of MRP1 and occurrence of MDR in leukemic patients. Furthermore, we wished to test the hypothesis that MRP1 polymorphisms would be predictive of MDR in patients with acute leukemia. mRNA level of MRP1 was determined in 111 patients with acute leukemia (including 52 patients with AML and 59 patients with ALL) by quantitative real time RT–PCR and compared to the type of response to chemotherapy. We typed G816A, T825C, G2168A, C2217T, G2268A, G1299T,G-260C, A-275G MRP1 polymorphisms in 24 patients classified as drug-resistant and normal control. We found that high expression of MRP1 was associated with MDR phenotype in both AML and ALL patients. There was no effect of a particular genotype on the expression level of the MRP1 gene. This could show the lack of dependency of any of these genotypes on the chemosensivity in this group of patients.