1. ¹Inserm, U503, Lyon, F-69007, France
2. ²Université de Lyon, Lyon, F-69003, France
3. ³Université Lyon 1, Lyon, F-69003, France
4. ⁴IFR128, Lyon, F-69007, France

Correspondence: Dr N Bonnefoy-Berard, Laboratoire d'Homéostasie Lymphocytaire, Inserm U503, 21 avenue Tony Garnier, Lyon 69007, France. E-mail: bonnefoy@cervi-lyon.inserm.fr

⁵These two authors contributed equally to this work.

Received 8 November 2006; Revised 14 December 2006; Accepted 24 January 2007; Published online 12 March 2007.

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.