Glucocorticoid resistance in paediatric acute lymphoblastic leukaemia

J Paediatr Child Health. 2012 Aug;48(8):634-40. doi: 10.1111/j.1440-1754.2011.02212.x. Epub 2011 Nov 3.

Abstract

Glucocorticoids (GCs), such as prednisolone and dexamethasone, are key components in multi-agent chemotherapy protocols used for the treatment of acute lymphoblastic leukaemia (ALL). Approximately 10% of children with ALL will respond poorly to GCs, and GC resistance is associated with a significantly inferior outcome. This review summarises the current knowledge of GC resistance in ALL, including the roles of the GC receptor and its co-chaperone molecules, the pro-apoptotic and pro-survival B-cell lymphoma 2 family members and alternative non-apoptotic mechanisms of cell death. It concludes with a discussion on therapeutic attempts to overcome GC resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Child
  • Drug Resistance, Neoplasm*
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use*
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • Glucocorticoids
  • Proto-Oncogene Proteins c-bcl-2