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Sensitivity, Resistance to Therapy and Apoptosis

Role of β2 integrins in the prevention of apoptosis induction in chronic lymphocytic leukemia B cells

Leukemia volume 14, pages 34–39 (2000)Cite this article

Abstract

Immunologically committed lymphocytes, especially mature, leukemic B cells, proliferate then accumulate without further cell division in chronic lymphocytic leukemia patients (CLL). These mature, leukemic B cells often produce autoantibodies. Under normal circumstances, immunologically committed lymphocytes that are autoreactive are deleted by a programmed cell death mechanism. In CLL cells, these mechanisms appear to be inhibited; therefore, cells accumulate rather than be destroyed. To understand the mechanism by which cell survival is selected over death in CLL cells, we studied the role of β2 integrins and their ligands in the regulation of apoptosis. CLL cells were treated with monoclonal antibodies directed against β2 integrins. Antibodies directed against the I-domain of the α chain of CD11b/CD18 inhibited apoptosis. The identity of the physiological ligand or counter-receptor for β2 integrins that was required for the inhibition of apoptosis induction was sought. The ligand iC3b, but not ICAM-1 or fibrinogen, was identified as a ligand that could prevent apoptosis of CLL B cells. Free iC3b levels were elevated in CLL patients indicating that this ligand is available in vivowhere it may interact with β2 integrins on CLL B cells and sustain their viability by preventing activation of the programmed cell death pathway. Leukemia (2000) 14, 34–39.

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Author notes

  1. BW Long

    Present address: University of Cincinnati Medical School, Cincinnati, OH, USA

  2. SB Kelkar

    Present address: University of Illinois at Chicago (UIC), Chicago, IL, USA

Authors and Affiliations

  1. Department of Medicine and the Rush Cancer Institute, Section of Medical Oncology, Rush-Presbyterian St Luke's Medical Center, Chicago, IL, USA

    JMD Plate, BW Long & SB Kelkar

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Plate, J., Long, B. & Kelkar, S. Role of β2 integrins in the prevention of apoptosis induction in chronic lymphocytic leukemia B cells. Leukemia 14, 34–39 (2000). https://doi.org/10.1038/sj.leu.2401621

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