| First Author | Nguyen HV | Year | 2020 |
| Journal | Blood | Volume | 135 |
| Issue | 13 | Pages | 1019-1031 |
| PubMed ID | 31978211 | Mgi Jnum | J:285934 |
| Mgi Id | MGI:6387376 | Doi | 10.1182/blood.2019003014 |
| Citation | Nguyen HV, et al. (2020) Development and Survival of MYC-driven Lymphomas Requires MYC Antagonist MNT to Curb MYC-induced Apoptosis. Blood 135(13):1019-31 |
| abstractText | Deregulated over-expression of MYC is implicated in the development and malignant progression of most (~70%) human tumors. MYC drives cell growth and proliferation but also, at high levels, promotes apoptosis. Here, we report that the proliferative capacity of MYC-driven normal and neoplastic B lymphoid cells depends on MNT, a MYC-related transcriptional repressor. Our genetic data establish that MNT synergises with MYC by suppressing MYC-driven apoptosis and that it does so primarily by reducing the level of pro-apoptotic BIM. In Em-Myc mice, which model the MYC/IGH chromosome translocation in Burkitt''s lymphoma, homozygous Mnt deletion greatly reduced lymphoma incidence by enhancing apoptosis and markedly decreasing premalignant B lymphoid cell populations. Strikingly, by inducing Mnt deletion within transplanted fully-malignant Em-Myc lymphoma cells, we significantly extended transplant recipient survival. The dependency of lymphomas on MNT for survival suggests that drugs inhibiting MNT could significantly boost therapy of MYC-driven tumors by enhancing intrinsic MYC-driven apoptosis. |
