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Title

THE ROLE OF MRP1 GENE ON DRUG RESISTANCE IN PEDIATRIC PATIENTS WITH ACUTE LUKEMIA

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Abstract

 Introduction: Occurrence of cross-resistance to structurally and functionally unrelated drugs, called Multidrug Resistance (MDR), is a main cause of failure in the chemotherapeutic treatment of malignant disorders. Several mechanisms of MDR have been identified; one of these mechanisms is the over expression of ATP-dependent membrane proteins that function as drug-efflux pumps. One of the well-known genes responsible for drug resistance is multidrug resistance-associated protein (MRP1) gene. The association of MRP1 with clinical drug resistance has been elaborated in some studies. No one systematically investigated the role of MRP1 gene in inducing MDR phenotype in Iranian pediatric leukemic patients. We aimed to use Real-Time RT-PCR technology to study the association between MRP1 gene and MDR phenotype in Iranian pediatric leukima patients.Methods: The expression level of MRP1 was determined by quantitative Real-time RT-PCR using total RNA isolated from peripheral blood of 39 ALL and 3AML and healthy individuals. The patients were divided into two groups, patients who response to chemotherapy and were in complete remission (CR), patients with no response to drug. The association between expression level of MRP1 and type of response to chemotherapy was investigated.Results:  We found that over expression of MRP1 occurred in most of the Iranian pediatric leukemia patients who do not response to chemotherapy treatments. The relation between MRP1 mRNA level and other clinical characteristics including cytogenetic subgroups and FAB subtypes was also investigated.Discussion:  We believe that in future it would be possible to use MRP1 gene as a prognostic factor in terms of induction therapy and overall survival.

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