INCREASED EXPRESSION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN GENE IN RELAPSED ACUTE-LEUKEMIA

Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine relative levels of transcripts for MDR1 and the recently described multidrug resistance-associated protein (MRP) in no rmal lymphohematopoietic cells and in 62 bone marrow aspirates of newl y diagnosed and recurrent acute leukemia. Levels of MRP expression in newly diagnosed AML samples were similar to those observed in normal b one marrow cells (CD34-negative and CD34-positive) and in unselected H F60 human promyelocytic leukemia cells, which were used as an internal control throughout this study. In contrast, samples of AML obtained a t the time of relapse contained approximately twofold higher levels of MRP RNA (P < .01). Analysis of paired samples, the first obtained at diagnosis and the second at relapse, from 13 acute myelogenous leukemi a (AML) and four acute lymphocytic leukemia (ALL) patients showed that MRP expression was increased at the time of relapse in greater than 8 0% of patients. In contrast, no consistent changes of MDR1 expression at relapse were observed. These results raise the possibility that inc reased MRP expression might contribute to leukemic relapse. This is a US government work. There are no restrictions on its use.