Multidrug resistance-associated protein (MRP) in haematological malignancies

Abstract

The presence of multidrug resistant cells, either acquired or de novo, severely limits treatment outcome in haematological malignancies. Although expression of the Mr 170,000 P-glycoprotein drug pump is likely to play a role in multidrug resistance (MDR) in haematological malignancies, it is now evident that other MDR mechanisms may be operational as well in leukaemias, lymphomas, and multiple myeloma. We determined the expression of a newly recognised drug resistance gene, the Multidrug Resistance-associated Protein (MRP) gene, in peripheral blood cells from healthy volunteers and from patients with haematological malignancies. Expression of MRP mRNA and its Mr 190,000 glycoprotein were estimated by RNase protection assay and immunocytochemistry, respectively. MRP appeared to be ubiquitously expressed at low levels in all nonmalignant haemopoietic cell types. However, some leukaemias showed elevated levels of MRP, probably due to transcriptional activation or increased mRNA stability. High to very high MRP expression levels were frequently found in chronic lymphocytic leukaemia and prolymphocytic leukaemia. Acute myelocytic leukemia often exhibited low but occasionally high MRP expression levels, while in the other acute and chronic leukaemias, lymphomas, and multiple myeloma, predominantly low, basal levels of MRP were found. We conclude that hyperexpression of MRP is observed in leukaemias, and that further studies are needed to assess the clinical relevance of MRP.