PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis

J Steroid Biochem Mol Biol. 2010 Jun;120(4-5):218-27. doi: 10.1016/j.jsbmb.2010.04.019. Epub 2010 May 6.


Glucocorticoids (GCs) cause cell cycle arrest and apoptosis in lymphoid cells which is exploited to treat lymphoid malignancies. The mechanisms of these anti-leukemic GC effects are, however, poorly understood. We previously defined a list of GC-regulated genes by expression profiling in children with acute lymphoblastic leukemia (ALL) during systemic GC monotherapy and in experimental systems of GC-induced apoptosis. PLZF/ZBTB16, a transcriptional repressor, was one of the most promising candidates derived from this screen. To investigate its role in the anti-leukemic GC effects, we performed overexpression and knock-down experiments in CCRF-CEM childhood ALL cells. Transgenic PLZF/ZBTB16 alone had no detectable effect on cell proliferation or survival, but reduced sensitivity to GC-induced apoptosis but not apoptosis induced by antibodies against Fas/CD95 or 3 different chemotherapeutics. Knock-down of ZBTB16 entailed a small, but significant, increase in cell death induction by GC. Affymetrix Exon array-based whole genome expression profiling revealed that PLZF/ZBTB16 induction did not significantly alter the expression profile, however, it interfered with the regulation of numerous GC response genes, including BCL2L11/Bim, which has previously been shown to be responsible for cell death induction in CCRF-CEM cells. Thus, the protective effect of PLZF/ZBTB16 can be attributed to interference with transcriptional regulation by GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Child
  • Gene Expression Regulation, Leukemic / drug effects*
  • Glucocorticoids / pharmacology*
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Promyelocytic Leukemia Zinc Finger Protein


  • Antineoplastic Agents
  • Glucocorticoids
  • Kruppel-Like Transcription Factors
  • Promyelocytic Leukemia Zinc Finger Protein
  • ZBTB16 protein, human