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Lymphoma

Lymphoma cell adhesion-induced expression of B cell-activating factor of the TNF family in bone marrow stromal cells protects non-Hodgkin's B lymphoma cells from apoptosis

Leukemia volume 23, pages 170–177 (2009)Cite this article

Abstract

This study explores whether lymphoma cell adhesion-induced B cell-activating factor (BAFF) expression in bone marrow stromal cells (BMSCs) protects B lymphoma cells from apoptosis. We first showed protection of lymphoma cells from apoptosis by conditioned medium of a stromal cell-lymphoma cell coculture, either spontaneous or induced by mitoxantrone, implying a role for soluble factor(s) in lymphoma cell survival. Addition of BAFF counteracted mitoxantrone-induced apoptosis and elicited a reduction in spontaneous apoptosis in primary lymphomas, suggesting a role of BAFF in sustaining B-cell survival. Abundant BAFF was detected in the BMSC cell line (HS-5) and primary BMSCs by flow cytometry, RT-PCR and immunoblotting. BAFF levels were 20- to 200-fold higher in BMSCs than in lymphoma cells, and lymphoma cell adhesion to BMSCs augmented BAFF secretion twofold through upregulation of BAFF gene expression. Finally, neutralization of BAFF by TACI-Ig or depletion of BAFF by small hairpin RNA (shRNA) in BMSCs significantly enhanced lymphoma cell response to chemotherapy and overcame stroma-mediated drug resistance, suggesting that lymphoma cells use BMSC-derived BAFF as a survival factor. These findings support the hypothesis that lymphoma cells interact with BMSCs, resulting in stromal niches with high BAFF concentration, and identify BMSC-derived BAFF as a functional determinant for B lymphoma cell survival in the bone marrow environment.

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Acknowledgements

This work was supported by grants from the American Cancer Society IRG 032 ACS (JT),the National Cancer Institute and the National Institute on Aging, and by a Cancer Pilot Research Grant (JT).

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Authors and Affiliations

  1. Department of Oncologic Sciences and Experimental Therapeutics Program, H. Lee Moffitt Cancer Center at the University of South Florida, Tampa, FL, USA

    T Lwin, L A Crespo, A Wu, S Dessureault, L C Moscinski, E Sotomayor, W S Dalton & J Tao

  2. Department of Virology, College of Life Sciences, Wuhan University, Wuhan, China

    H B Shu

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  1. T Lwin
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  2. L A Crespo
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  3. A Wu
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  7. E Sotomayor
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  8. W S Dalton
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Correspondence to J Tao.

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Lwin, T., Crespo, L., Wu, A. et al. Lymphoma cell adhesion-induced expression of B cell-activating factor of the TNF family in bone marrow stromal cells protects non-Hodgkin's B lymphoma cells from apoptosis. Leukemia 23, 170–177 (2009). https://doi.org/10.1038/leu.2008.266

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