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Chronic Lymphocytic Leukemia (CLL)

CD5-induced apoptosis of B cells in some patients with chronic lymphocytic leukemia

Leukemia volume 16, pages 44–52 (2002)Cite this article

Abstract

Although B chronic lymphocytic leukemia (B-CLL) is characterized by prolonged survival of CD5+ B cells in vivo, these cells apoptose spontaneously in vitro. The effect of CD5 ligation on apoptosis was studied in 27 newly diagnosed patients with B-CLL, in relation to the expression of surface IgM (sIgM), CD79b, CD38, CD72 and CD19. B cells from 15 patients (group I) were resistant to anti-CD5-induced apoptosis, whereas apoptosis above spontaneous levels was seen in the remaining 12 studied (group II). Group II was then subdivided on the basis of differences in the time required to reach maximum apoptosis: whilst B cells from seven patients underwent apoptosis by 18 h, those from the remaining five needed 36 h to apoptose. The expression of sIgM, CD5, CD79b and CD38 was higher in group II than group I, suggesting that signaling for apoptosis might operate via CD79, and that CD38 expression was required. As shown by flow cytometry and confirmed by Western blotting, apoptosis was associated with a decrease in the ratios of Bcl-2/Bax and BclXL/Bax, due to an increase in the level of Bax, but no change in that of Bcl-2. This heterogeneous apoptotic response to CD5 ligation offers an explanation for the incomplete success of anti-CD5 monoclonal therapy, and might help identify patients who would respond to such treatment.

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Acknowledgements

We thank Professors M Bourel, JL Binet (Académie Nationale Française de Médecine, Paris, France), F Caligaris-Cappio (Università di Torino, Torino, Italy) and JL Preud'homme (CNRS, Poitiers, France) for critical reading of the manuscript. We are also indebted to Professors M Hirn (Immunotech, Marseilles, France) and PC Beverley (Jenner Institute for Vaccine Development, Compton, UK) who provided reagents, and to Ms S Hamon and S Forest for secretarial assistance. This work was supported by the ‘Académie Nationale Française de Médecine’ and the ‘Comité du Finistère de la Ligue Nationale contre le Cancer’, and an INTAS European Community grant.

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  1. Institut de Synergie des Sciences et de la Santé, Brest University Medical School, Brest, France

    JO Pers, C Berthou, M Burdjanadze, G Le Calvez, JF Abgrall, P Youinou & C Jamin

  2. Department of Immunology, Royal Free and University College Medical School, London, UK

    N Porakishvili & PM Lydyard

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Pers, J., Berthou, C., Porakishvili, N. et al. CD5-induced apoptosis of B cells in some patients with chronic lymphocytic leukemia. Leukemia 16, 44–52 (2002). https://doi.org/10.1038/sj.leu.2402327

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