Send to

Choose Destination
See comment in PubMed Commons below
Blood. 2010 Feb 4;115(5):995-1005. doi: 10.1182/blood-2009-03-212670. Epub 2009 Dec 3.

Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad.

Author information

  • 1Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.


Oncogenic c-Myc is known to balance excessive proliferation by apoptosis that can be triggered by p53-dependent and p53-independent signaling networks. Here, we provide evidence that the BH3-only proapoptotic Bcl-2 family members Bcl-2 modifying factor (Bmf) and Bcl-2 antagonist of cell death (Bad) are potent antagonists of c-Myc-driven B-cell lymphomagenesis. Tumor formation was preceded by the accumulation of preneoplastic pre-B and immature immunoglobulin M-positive (IgM(+)) B cells in hematopoietic organs of Emu-myc/bmf(-/-) mice, whereas Emu-myc/bad(-/-) mice showed an increase of pre-B cells limited to the spleen. Although the loss of Bad had no impact on the tumor immunophenotype, Bmf deficiency favored the development of IgM(+) B cell over pre-B cell tumors. This phenomenon was caused by a strong protection of immature IgM(+) B cells from oncogene-driven apoptosis caused by loss of bmf and c-Myc-induced repression of Bmf expression in premalignant pre-B cells. Steady-state levels of B-cell apoptosis also were reduced in the absence of Bad, in support of its role as a sentinel for trophic factor-deprivation. Loss of Bmf reduced the pressure to inactivate p53, whereas Bad deficiency did not, identifying Bmf as a novel component of the p53-independent tumor suppressor pathway triggered by c-Myc.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk