| First Author | Happo L | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 24 | Pages | 5256-67 |
| PubMed ID | 20829369 | Mgi Jnum | J:167411 |
| Mgi Id | MGI:4868181 | Doi | 10.1182/blood-2010-04-280818 |
| Citation | Happo L, et al. (2010) Maximal killing of lymphoma cells by DNA damage-inducing therapy requires not only the p53 targets Puma and Noxa, but also Bim. Blood 116(24):5256-67 |
| abstractText | DNA-damaging chemotherapy is the backbone of cancer treatment, although it is not clear how such treatments kill tumor cells. In nontransformed lymphoid cells, the combined loss of 2 proapoptotic p53 target genes, Puma and Noxa, induces as much resistance to DNA damage as loss of p53 itself. In Emu-Myc lymphomas, however, lack of both Puma and Noxa resulted in no greater drug resistance than lack of Puma alone. A third B-cell lymphoma-2 homology domain (BH)3-only gene, Bim, although not a direct p53 target, was up-regulated in Emu-Myc lymphomas incurring DNA damage, and knockdown of Bim levels markedly increased the drug resistance of Emu-Myc/Puma(-/-)Noxa(-/-) lymphomas both in vitro and in vivo. Remarkably, c-MYC-driven lymphoma cell lines from Noxa(-/-)Puma(-/-)Bim(-/-) mice were as resistant as those lacking p53. Thus, the combinatorial action of Puma, Noxa, and Bim is critical for optimal apoptotic responses of lymphoma cells to 2 commonly used DNA-damaging chemotherapeutic agents, identifying Bim as an additional biomarker for treatment outcome in the clinic. |
