Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India

Abstract

 In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTπ, and GSTμ. The expression of β₂ microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTπ, and in 19 for GSTμ. The values ranged from undetectable to 132% of the control A549 cell line for MRP, undetectable to 49% of the HL60/DNR control cell line for MDR1, undetectable to 268% of A549 control cell line for GSTπ, and undetectable to 247% of A549 control cell line for GSTμ mRNA. Increased MRP levels were associated with increased GSTπ and GSTμ levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTπ levels (p<0.05). The present observations showed no correlation between the MDR1 and MRP values with treatment outcome, in terms of either achieving a complete remission or predilection to early relapse. In view of some recent studies that envisage MRP as an energy-dependent pump involved in the efflux of GSH conjugates, the simultaneous up-regulation of transcription of all these genes might well be part of an integrated detoxification response that has been switched on after exposure to an environmental stress.