| First Author | Frenzel A | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 5 | Pages | 995-1005 |
| PubMed ID | 19965635 | Mgi Jnum | J:156718 |
| Mgi Id | MGI:4421262 | Doi | 10.1182/blood-2009-03-212670 |
| Citation | Frenzel A, et al. (2010) Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad. Blood 115(5):995-1005 |
| abstractText | 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. |
