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Cancer Immunology, Immunotherapy

, Volume 63, Issue 1, pp 37–43 | Cite as

Non-genomic events determining the sensitivity of hemopoietic malignancies to glucocorticoid-induced apoptosis

  • Shlomit Kfir-ErenfeldEmail author
  • Eitan Yefenof
Focussed Research Review

Abstract

Glucocorticoid (GC) hormones have been introduced as therapeutic agents in blood cancers six decades ago. The effectiveness of GC treatment stems from its ability to induce apoptotic death of hemopoietic cells. A major impediment in GC therapy is the acquisition of resistance to the drug upon repeated treatment. In addition, some blood cancers are a priori resistant to GC therapy. Usually, resistance to GC correlates with poor prognosis. Albeit the wide use of GC in clinical practice, their mode of action is not fully understood. The cellular response to GC is initiated by its binding to the cytosolic GC receptor (GR) that translocates to the nucleus and modulates gene expression. However, nuclear activities of GR occur in both apoptosis-sensitive and apoptosis-resistant cells. These apparent controversies can be resolved by deciphering non-genomic effects of GCs and the mode by which they modulate the apoptotic response. We suggest that non-genomic consequences of GC stimulation determine the cell fate toward survival or death. Understanding the cellular mechanisms of GC apoptotic sensitivity contributes to the development of new modalities for overcoming GC resistance.

Keywords

Glucocorticoids Hemopoietic tumors Mitochondria BIM Glycogen synthase kinase 3 CITIM 2013 

Notes

Acknowledgments

The authors wish to thank Dr. Ronit Vogt-Sionov, Hali Spokoini, and Prof. Ingrid Herr for their contribution. The study described in this review was supported in part by the German-Israel Foundation (GIF) and Concern Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.The Lautenberg Center for Immunology and Cancer Research, IMRICThe Hebrew University-Hadassah Medical SchoolJerusalemIsrael

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