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Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis

Oncogene volume 26, pages 5828–5832 (2007)Cite this article

Abstract

Elevated expression of the antiapoptotic protein Bfl-1 (A1) was previously reported in several cancer cell lines. Recently, molecular profiling of large B-cell lymphoma identified Bfl-1 as a gene signature in ‘OxPhos’ diffuse large B-cell lymphoma subtype and in primary mediastinal large B-cell lymphoma, suggesting that in addition to Bcl-2, Bcl-xL and Mcl-1, Bfl-1 may be a relevant target in the design of new strategies for cancer therapy. Using short hairpin RNA strategy, we show here that Bfl-1 silencing in one lymphoblastoid B-cell line and in two diffuse large B-cell lymphoma cell lines potently induces their apoptosis and sensitizes those cell lines to anti-CD20 (Rituximab)-mediated cell death as well as to apoptosis induced by chemotherapeutic molecules such as doxorubicin, vincristine, cisplatin and fludarabine. These results demonstrate for the first time that Bfl-1 is an essential protein for survival of malignant B cells and suggest Bfl-1 may represent a potential target for future drug development against B cell lymphoma.

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Abbreviations

BCR:

B-cell receptor

DLBCL:

diffuse large B-cell lymphoma

GFP:

green fluorescent protein

MLBCL:

mediastinal large B-cell lymphoma

MOI:

multiplicity of infection

shRNA:

short hairpin RNA

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Acknowledgements

This work is support by institutional grants from INSERM and université Lyon I, and additional support from the Association pour la Recherche sur le Cancer, the Ligue contre le Cancer (comité de Savoie et de la Drôme) and Cancéropole National. G Brien was supported by a fellowship from the région Rhône-Alpes and is now supported by a fellowship from the Ligue Nationale contre le Cancer. We thank Dr C Thieblemont for critical reading of the paper and Dr C Dumontet for helpful discussions, C Bella and O de Bouteiller for their expertise with cell sorting and D Nègre and B Boson for production of lentivirus particules.

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Author notes

  1. G Brien and M-C Trescol-Biemont: These two authors contributed equally to this work.

Authors and Affiliations

  1. Inserm, U503, Lyon, F-69007, France

    G Brien, M-C Trescol-Biemont & N Bonnefoy-Bérard

  2. Université de Lyon, Lyon, F-69003, France

    G Brien, M-C Trescol-Biemont & N Bonnefoy-Bérard

  3. Université Lyon 1, Lyon, F-69003, France

    G Brien, M-C Trescol-Biemont & N Bonnefoy-Bérard

  4. IFR128, Lyon, F-69007, France

    G Brien, M-C Trescol-Biemont & N Bonnefoy-Bérard

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  1. G Brien
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Correspondence to N Bonnefoy-Bérard.

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Brien, G., Trescol-Biemont, MC. & Bonnefoy-Bérard, N. Downregulation of Bfl-1 protein expression sensitizes malignant B cells to apoptosis. Oncogene 26, 5828–5832 (2007). https://doi.org/10.1038/sj.onc.1210363

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