Abstract for presentation at 11th International Congress of Human Genetics

Multidrug resistance (MDR) is one of the main obstacles in treatment of cancer patients. Therefore it has been studied for half a century now, ever since cytotoxic drugs were first used for cancer therapy. So far, about three separate forms of MDR have been characterized in more detail: classical MDR, non-Pgp MDR and atypical MDR. The classical MDR phenotype is characterized by a reduced ability to accumulate drugs. The classical MDR drug pump is composed of a transmembrane glycoprotein (P-glyco-protein-Pgp) encoded by the so-called multidrug resistance (MDR1) gene. Typically, non-Pgp MDR has no P-gly-coprotein expression, yet has about the same cross-resistance pattern as classical MDR. This non-Pgp MDR phenotype is caused by over-expression of the multidrug resistance-associated protein (MRP1) gene.
The association of MRP1 with clinical drug resistance has been elaborated in some studies. To the best of our knowledge (although one of the main obstacles in chemotherapy success rate) no one systematically investigated the role of MRP1 gene in inducing MDR phenotype in Iranian leukemic patients. By employing chromosome microdissection we shown that increased in gene copy number and also over-expression of MRP1 gene are involved in drug resistance in a drug resistance leukemia cell line.
In addition, we have used fluorescent in situ hybridization (FISH) and Real-Time PCR technology to study the association between MRP1 and MDR phenotype in Iranian AML patients. So far we found that over-expression of MRP1 occurs in about 20% of the Iranian AML patients. We are aiming to further investigate whether or not elevated MRP expression in Iranian patients at diagnosis is an unfavorable prognostic factor for clinical outcome of chemotherapy.