EXPRESSION OF THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) IN ACUTE AND CHRONIC LEUKEMIAS

We determined the expression of the multidrug resistance-associated pr otein (MRP), a new putative transmembrane drug transporter, in periphe ral blood cells from healthy volunteers as well as from 60 patients wi th acute or chronic leukemia, using an RNase protection assay. MRP app eared to be ubiquitously expressed at low levels in all nonmalignant h emopoietic cell types, reflecting its basal constitutive expression. I n acute myelocytic leukemia (AML) (n = 16), one of nine untreated pati ents and two of seven patients with prior chemotherapy showed signific ant hyperexpression of MRP. In chronic lymphocytic leukemia (CLL) (n = 21), either treated (n = 8) or untreated (n = 13), a high percentage (15 of 21) 71% had relatively high expression levels of the MRP gene. In contrast, low MRP expression levels were detected in acute lymphocy tic leukemia (n = 14), and in chronic myelocytic leukemia (n = 9). DNA analysis by Southern blotting did not reveal amplification of the MRP gene in the leukemia samples, including those with elevated MRP mRNA levels. We conclude that relatively high expression of MRP is occasion ally observed in AML and at high frequency in CLL, irrespective of tre atment, probably due to transcriptional activation and/or increased mR NA stability.