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

Ann Hematol. 1998 May;76(5):195-200. doi: 10.1007/s002770050388.

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, GSTpi, and GSTmu. The expression of beta2 microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTpi, and in 19 for GSTmu. 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 GSTpi, and undetectable to 247% of A549 control cell line for GSTmu mRNA. Increased MRP levels were associated with increased GSTpi and GSTmu levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTpi 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adolescent
  • Adult
  • Age Factors
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression
  • Genes, MDR / genetics
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics
  • Humans
  • Immunophenotyping
  • India
  • Infant
  • Isoenzymes / genetics
  • Leukocyte Count
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins
  • Polymerase Chain Reaction
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • RNA, Messenger / analysis
  • Sex Factors
  • Treatment Outcome

Substances

  • ATP-Binding Cassette Transporters
  • Isoenzymes
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase