Multidrug Resistance in Myelodysplastic Syndromes and Acute Leukemia

Abstract

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of acquired clonal bone marrow disorders with an increased risk of transformation to acute myeloid leukemia (AML). In these disorders, aggressive chemotherapy usually yields results inferior to those achieved in de novo AML [1]. The biological basis of the reduced responsiveness of the preleukemic cell clone to chemotherapy is unknown. However, evidence from cytogenetic and epidemiological studies suggests that it may be related to potential differences in tumor initiation and/or progression. Increased drug resistance and expression of the multidrug resistance (MDR) phenotype, designated as Pglycoprotein, have been observed in hemopoietic cells of patients with MDS and AML prior to exposure to cytotoxic therapy [2]. It has been demonstrated that the frequence of gene mutations increases with progression of MDS [3]. Observations of Kadoyama [4] implicating the participation of protooncogenes in the regulation of MDR suggest that acquisition of proliferative signals promote P-glycoprotein expression in such cases. P-glycoprotein mediates the resistance to multiple, structurally dissimilar drugs including anthracyclines, actinomycin D, vinca alkaloids, and epipodophyllotoxins. As these substances represent integral components of antileukemic regimens, we tried to determine the prognostic value of MDR expression in patients with advanced MDS or de novo acute leukemia undergoing aggressive chemotherapy.