Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells: Relation to early gene expression

Leuk Res. 2009 Dec;33(12):1684-95. doi: 10.1016/j.leukres.2009.04.018. Epub 2009 May 18.

Abstract

Resistance or sensitivity to glucocorticoids is considered to be of crucial importance for disease prognosis in childhood acute lymphoblastic leukemia. Prednisolone exerted a delayed biphasic effect on the resistant CCRF-CEM leukemic cell line, necrotic at low doses and apoptotic at higher doses. At low doses, prednisolone exerted a pre-dominant mitogenic effect despite its induction on total cell death, while at higher doses, prednisolone's mitogenic and cell death effects were counterbalanced. Early gene microarray analysis revealed notable differences in 40 genes. The mitogenic/biphasic effects of prednisolone are of clinical importance in the case of resistant leukemic cells. This approach might lead to the identification of gene candidates for future molecular drug targets in combination therapy with glucocorticoids, along with early markers for glucocorticoid resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Primers
  • Gene Expression / drug effects*
  • Humans
  • Mitogens / pharmacology*
  • Oligonucleotide Array Sequence Analysis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Prednisolone / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • Mitogens
  • Prednisolone