Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia cells

Leukemia Research
Piotr SmolewskiTadeusz Robak

Abstract

Inhibitor of proteasome, bortezomib (BOR), although highly active in vitro, showed unexpectedly low efficacy in vivo in patients with B-CLL when used alone. We studied the in vitro cytotoxic effects of BOR in combination with anti-CD20 (rituximab, RIT) or anti-CD52 (campath, CAM) monoclonal antibodies on B-CLL cells. Both BOR+RIT and BOR+CAM combinations exerted additive cytotoxicity, triggering caspase-dependent apoptosis. The treatment significantly modified expression of several apoptosis-regulating proteins, including upregulation of Bax or downregulation of Bcl-2 and Mcl-1 by BOR+RIT, as well as downregulation of Bcl-2 and XIAP by BOR+CAM. These data suggest the feasibility of concomitant use of those agents for the treatment of B-CLL patients.

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Citations

Nov 11, 2006·Leukemia·A NencioniP Brossart
Apr 27, 2012·Patient Preference and Adherence·Danielle M Brander, Anne W Beaven
Sep 16, 2011·Leukemia & Lymphoma·Tri-Hung NguyenSrinivas Shankara
Sep 1, 2009·Clinical Lymphoma & Myeloma·John P LeonardJohn W Sweetenham
Oct 30, 2010·Clinical Lymphoma, Myeloma & Leukemia·Michael E WilliamsJohn P Leonard
Sep 23, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sven de VosAnthony L Boral
Apr 24, 2013·Therapeutic Advances in Hematology·Michele MerliFrancesco Passamonti
May 15, 2012·International Journal of Oncology·Lian-Nv QiuWei-Xiao Hu
Mar 12, 2017·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Yang ZhaoYong Zhao
Jun 5, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven P TreonAshraf Badros
Aug 5, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John J Wright

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