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Non-malignant leukocytes delay spontaneous B-CLL cell apoptosis

Leukemia volumeĀ 15,Ā pages 1860ā€“1867 (2001)Cite this article

Abstract

Malignant B cells from chronic lymphocytic leukemia (B-CLL) patients have a long survival in vivo, although, in culture, they spontaneously die by apoptosis. Here, we analyzed the capacity of accessory leukocytes to modulate apoptosis of B-CLL cells in vitro. To this end, we performed long-term cultures using total mononuclear cells (TMC) from B-CLL patients and TMC depleted from monocytes, NK cells and T lymphocytes (B-CLL cells). In all the patients studied (nā€‰=ā€‰25) the presence of accessory leukocytes markedly prolonged the survival of B-CLL cells. The anti-apoptotic effect was exerted by monocytes and, to a lesser degree, NK cells, partially through the release of soluble factors. Indeed, accessory leukocytes separated from leukemic cells by semipermeable membranes were still able to prolong B-CLL cell survival. By flow cytometric analysis we found that the protective effect of non-malignant cells was associated with delayed down-regulation of Bcl-2 expression on leukemic cells. By contrast, the expression of Fas and Fas ligand proteins was unchanged in most samples. Our findings suggest that monocytes and NK cells, by delaying leukemic cell apoptosis, may play a role in B-CLL cell accumulation in vivo.

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Acknowledgements

We would like to thank Ms Selma Tolosa and Ms Nelly Villagra for their excellent technical assistance and FundaciĆ³n de la Hemofilia for the use of the FACScan cytometer. This work was supported by grants from Consejo Nacional de Investigaciones Cientificas y TĆ©cnicas, Agencia-Foncyt, Buenos Aires University School of Medicine, Ministerio de Salud and FundaciĆ³n Alberto J Roemmers.

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Authors and Affiliations

  1. Laboratory of Immunology, Institute of Haematologic Research, National Academy of Medicine, Buenos Aires, Argentina

    R Gamberale,Ā J Geffner,Ā G Arrosagaray,Ā M Scolnik,Ā G Salamone,Ā A Trevani,Ā M VermeulenĀ &Ā M Giordano

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  1. R Gamberale
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  2. J Geffner
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Gamberale, R., Geffner, J., Arrosagaray, G. et al. Non-malignant leukocytes delay spontaneous B-CLL cell apoptosis. Leukemia 15, 1860ā€“1867 (2001). https://doi.org/10.1038/sj.leu.2402288

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