Molecular determinants of glucocorticoid sensitivity and resistance in acute lymphoblastic leukemia

W. J.E. Tissing*, J. P.P. Meijerink, M. L. den Boer, R. Pieters

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

125 Citations (Scopus)

Abstract

Glucocorticoids (GC) are probably the most important drugs in the treatment of ALL. Despite the extensive use of GC for many years, little is known about the molecular mechanisms of sensitivity and resistance. This review summarizes the knowledge on GC cytotoxicity in leukemia. The relevance of polymorphisms, splice variants and the number and regulation of the GC receptor are discussed. The role of multidrug resistance proteins, glutathione and glutathione S-transferase is evaluated, as well as the influence of the different heat-shock chaperone (hsp 90 and 70) and co-chaperone proteins (BAG-1 and others) which form a complex together with the GC receptor. Finally, the transactivation and transrepression (via NF-κB and AP-1 binding) of a wide range of genes (like c-myc) which initiates the final apoptosis pathway are discussed and suggestions for future directions of research in ALL patients are given.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalLeukemia
Volume17
Issue number1
DOIs
Publication statusPublished - 1 Jan 2003

Keywords

  • Acute lymphoblastic leukemia
  • Apoptosis
  • Childhood
  • Glucocorticoid
  • Glucocorticoid receptor
  • Resistance

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