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Apoptosis induction by hypercross-linking of the surface antigen CD5 with anti-CD5 monoclonal antibodies in B cell chronic lymphocytic leukemia

Leukemia volume 16, pages 335–343 (2002)Cite this article

Abstract

We evaluated cells from 24 patients with B cell chronic lymphocytic leukemia (B-CLL) to determine apoptosis induced by CD5 hypercross-linking. Following the CD5 hypercross-linking with anti-CD5 monoclonal antibodies (MoAbs), we identified 10 patients where CD5 hypercross-linking induced apoptosis (group A) and 14 patients whose cells were resistant to the anti-CD5 MoAbs (group B). The programmed cell death pathway of the cells from patient group A was caspase-3 and poly (ADP-ribose) polymerase (PARP)-dependent, involved a reduction of the mitochondrial transmembrane potential ΔΨ and a down-regulation of the anti-apoptotic Bcl-2, Mcl-1 and iNOS proteins. Early activation-associated molecules such as CD25 and CD69 were expressed at higher levels than in controls after 6 h of culture with anti-CD5 MoAb. The expression of CD5 and of CD72, the ligand for CD5, were significantly lower in group A compared with group B. Anti-CD20 MoAb had similar activity with anti-CD5 MoAb and the combination of the two MoAbs seemed to be additive. In this study, it is suggested that the cells from some B-CLL patients can be induced into programmed cell death by CD5 hypercross-linking with anti-CD5 MoAbs.

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Acknowledgements

We thank Professor Kendo Kiyosawa for valuable advice and Dr Fumihiro Ishida for constructive discussion. We also thank Mr Susumu Ito for technical assistance and Drs Mayumi Ueno, Shigetaka Shimodaira, Shojiro Takagi, Naohiko Chiba, Hiroshi Morishita, Shigeki Seki, Naoaki Ichikawa, Toshiro Ito, Hikaru Kobayashi and Hiroshi Saito for providing patient samples.

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  1. Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan

    DP Cioca & K Kitano

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Cioca, D., Kitano, K. Apoptosis induction by hypercross-linking of the surface antigen CD5 with anti-CD5 monoclonal antibodies in B cell chronic lymphocytic leukemia. Leukemia 16, 335–343 (2002). https://doi.org/10.1038/sj.leu.2402393

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