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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects*
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Apoptosis / physiology
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Caspases / metabolism
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Cisplatin / pharmacology
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Down-Regulation
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Doxorubicin / pharmacology
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Drug Resistance, Neoplasm*
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology*
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Humans
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Lymphoma, B-Cell / genetics
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Lymphoma, B-Cell / pathology*
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Minor Histocompatibility Antigens
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Small Interfering / pharmacology
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Rituximab
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Tumor Cells, Cultured / drug effects
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Vidarabine / analogs & derivatives
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Vidarabine / pharmacology
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Vincristine / pharmacology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents
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BCL2-related protein A1
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Minor Histocompatibility Antigens
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Proto-Oncogene Proteins c-bcl-2
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RNA, Small Interfering
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Rituximab
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Vincristine
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Doxorubicin
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Caspases
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Vidarabine
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fludarabine
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Cisplatin