Glutathione-s-transferase pi expression in leukaemia: a comparative analysis with mdr-1 data

Abstract

Drug resistance in haemopoietic cells may be partly related to the expression of the glutathione-s-transferase (GST) pi and mdr-1 genes. We have used RNA slot blotting techniques to investigate the expression of GST pi in peripheral blood and bone marrow of eleven normal subjects, nine patients with myelodysplastic syndrome (MDS), eighteen patients with acute myeloblastic leukaemia (AML), and thirty-two patients with chronic lymphocyte leukaemia (CLL). We found increased expression of GST pi in 8 of 9 MDS, (7 peripheral blood, 1 bone marrow) 12 of 18 AML (5 peripheral blood, 7 bone marrow; 4 of 5 untreated, 1 of 5 secondary, 7 of 11 relapse or refractory) and in the peripheral blood of 24 of 32 CLL (3 of 7 untreated, 21 of 25 treated) relative to normal controls. Increased expression of GST pi can occur at any stage of disease and shows no clear relation to mdr-1 expression except, possibly, in CLL. In 3 AML patients GST pi transcript levels were the same or lower on relapse compared to presentation. Upregulation of the GST pi gene could not be demonstrated in 2 CLL patients in response to treatment with intermittent chlorambucil.