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MRP1 protein expression in leukemic stem cells as a negative prognostic marker in acute myeloid leukemia patients.

ABSTRACT

It is well established that expression of multi-drug resistance (MDR) proteins (MDR1, BCRP, MDR3, MRP1 and LRP) in leukemic blasts correlates with AML patients clinical response. Assuming that leukemic stem cells (LSC) are resistant to chemotherapy and responsible for relapse it might be clinically relevant to evaluate the expression level of MDR proteins in LSC and relate it to the clinical outcome.Bone marrow samples from 26 patients with de novo AML were labeled with antibodies to distinguish CD34+CD38-CD123+ LSC population and with antibodies against MDR1, BCRP, MDR3, MRP1 or LRP proteins. Multicolor flow cytometry was applied to evaluate the expression of MDR proteins in blasts and LSC.Nine of 26 patients with AML attained CR (30%). High negative correlation was found between MDR1 and LRP expression in blasts and the patients remission. MDR proteins were expressed more frequently in LSC than in leukemic blasts. High negative correlation was also observed between remission achievement and MRP1 expression in LSC.Our data presents for the very first time the high negative correlation between MRP1 protein expression in LSC and AML patients' remission. It does strongly suggest that MRP1 expression in LSC is an adverse prognostic marker in patients with de novo AML. This article is protected by copyright. All rights reserved.