Multidrug resistance in haemopoietic cell lines, myelodysplastic syndromes and acute myeloblastic leukaemia

Abstract

Resistance to cytotoxic agents is a common clinical problem encountered in the treatment of human myelodysplastic syndromes (MDS) and acute myeloblastic leukaemia (AML). Cellular acquisition of the multidrug resistance (MDR) phenotype confers loss of sensitivity to a wide range of structurally dissimilar anti-neoplastic agents. This state can arise through increased expression of the mdrl (P-glycoprotein) gene. We have used the mdrl gene probe to investigate adriamycin resistant (HL60/AR) and vinblastine resistant (CEM/VLB100) human leukaemic cell lines. In addition, peripheral blood or bone marrow cells from 66 patients with MDS and AML have been screened for gene amplification and 40 cases for increased mRNA expression. P-glycoprotein gene amplification was observed only in the (CEM/VLB100) and not in the HL60/AR on any other leukaemic cell line. Gene amplification was not found in any patient's cells. Eighteen out of 40 patients showed an increase (2----20) of mdrl mRNA expression. These results are not only of significance in understanding the biology of human drug resistance but have practical importance in the design of anti-leukaemic therapy.