Development and survival of MYC-driven lymphomas require the MYC antagonist MNT to curb MYC-induced apoptosis
- Author(s)
- Nguyen, HV; Vandenberg, CJ; Ng, AP; Robati, MR; Anstee, NS; Rimes, J; Hawkins, ED; Cory, S;
- Details
- Publication Year 2020-03-26,Volume 135,Issue #13,Page 1019-1031
- Journal Title
- Blood
- Publication Type
- Journal Article
- Abstract
- Deregulated overexpression of MYC is implicated in the development and malignant progression of most ( approximately 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 synergizes with MYC by suppressing MYC-driven apoptosis, and that it does so primarily by reducing the level of pro-apoptotic BIM. In Emu-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 Emu-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.
- Research Division(s)
- Blood Cells And Blood Cancer; Inflammation
- PubMed ID
- 31978211
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7118401/
- Publisher's Version
- https://doi.org/10.1182/blood.2019003014
- NHMRC Grants
- NHMRC/1060179, NHMRC/1122783,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-05-04 03:01:38
Last Modified: 2020-05-04 03:03:59