Adding Velcade to Rituximab or Campath Gives Better Results than Velcade Alone

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Leukemia Research

Article in Press, Corrected Proof - Note to users

Abstract

Copyright © 2006 Elsevier Ltd All rights reserved.

Additive cytotoxic effect of bortezomib in combination with anti-CD20

or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia

cells

Piotr Smolewskia, 1, , , Markus Duechlerb, c, 1, Linkea, Barbara

Cebulaa, Olga Grzybowska-Izydorczyka, Medhat Shehatab and Tadeusz

Robaka

aDepartment of Hematology, Medical University of Lodz, Poland

bLudwig Boltzmann Institute for Cytokine Research, Department of

Hematology, Clinic of Internal Medicine I, AKH Vienna, Austria

cNofer Institute of Occupational Medicine, Department of Toxicology

and Carcinogenesis, Lodz, Poland

Received 3 February 2006; revised 8 March 2006; accepted 13 March

2006. Available online 19 April 2006.

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.