alexa Alemtuzumab induces enhanced apoptosis in vitro in B-cells from patients with chronic lymphocytic leukemia by antibody-dependent cellular cytotoxicity.
Immunology

Immunology

Journal of Clinical & Cellular Immunology

Author(s): Nckel H, Frey UH, Rth A, Dhrsen U, Siffert W

Abstract Share this page

Abstract Alemtuzumab, a monoclonal anti-CD52 antibody has been shown to be highly effective in B-cell chronic lymphocytic leukemia, even in fludarabine-refractory disease. The mechanism of action is currently unknown, but may rely on complement-mediated cell lysis and antibody-dependent cellular cytotoxicity. The aim of this study was to assess the proapoptotic activity of alemtuzumab in chronic lymphocytic leukemia and to describe pathways potentially underlying this effect. Peripheral blood mononuclear cells from 21 chronic lymphocytic leukemia patients were treated in vitro in the absence of complement with fludarabine alone, alemtuzumab alone, or with the additional presence of a cross-linking anti-Fc-antibody. Apoptosis was quantified after 24 h by flow cytometry analysis. Expression of several pro- and anti-apoptotic proteins was determined at different time points. Apoptosis of peripheral blood mononuclear cells treated with alemtuzumab alone was significantly enhanced compared to untreated cells suggesting a minor potentially cytotoxic mechanism by direct signaling independent from antibody-dependent cellular cytotoxicity. The presence of a cross-linking anti-Fc-antibody induced the formation of cell clusters and enhanced apoptosis significantly suggesting a potential role of antibody-dependent cellular cytotoxicity in alemtuzumab induced apoptosis. Alemtuzumab activated a CD52-dependent signaling pathway which induced a significant increase in caspase 3 and 8 expression. Alemtuzumab significantly enhances apoptosis in chronic lymphocytic leukemia cells in vitro, especially in combination with a cross-linking anti-Fc-antibody, this effect being mediated by a caspase-dependent pathway. This article was published in Eur J Pharmacol and referenced in Journal of Clinical & Cellular Immunology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords