Disruption of the IFN-γ cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis

Zaki, Mohamed; Douglas, Raymond; Patten, Nancy; Bachinsky, Margaret; Lamb, Roberta; Nowell, Peter; Moore, Jonni

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Volume 24, Issue 7 , Pages 611-621, July 2000

Disruption of the IFN-γ cytokine network in chronic lymphocytic leukemia contributes to resistance of leukemic B cells to apoptosis☆

Mohamed Zaki
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
- Ain Shams University, Cairo, Egypt
Raymond Douglas
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
Nancy Patten
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
Margaret Bachinsky
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
Roberta Lamb
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
Peter Nowell
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
Jonni Moore
- Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, USA
- Corresponding author. Tel.: +1-215-8986853; fax: +1-215-8984227

Received 12 August 1999; accepted 27 January 2000.

Abstract

Recent evidence indicates that the slowly expanding population of CD5+ B cells that characterizes chronic lymphocytic leukemia (CLL) results primarily from defects in responses to cytokines that regulate apoptosis (e.g. I1-4, TGF-β, IFN-α, IFN-γ). We have now demonstrated not only that the enhanced anti-apoptotic effect of IFN-γ on these neoplastic B cells is apparently mediated through increased levels of IFN-γ receptors but also that there are increased numbers of IFN-γ-expressing CD4 and CD8 T cells in these patients. This is the strongest evidence to date that multiple alterations in the IFN-γ cytokine network contribute to the pathogenesis of CLL.

Keywords: Chronic lymphocytic leukemia, Cytokines, IFN-γ, Apoptosis, Flow cytometry, Immunoregulation, T lymphocytes

Abbreviations: CLL, chronic lymphocytic leukemia, IFN-γ, interferon gamma