MNT suppresses T cell apoptosis via BIM and is critical for T lymphomagenesis
- Author(s)
- Nguyen, HV; Vandenberg, CJ; Robati, MR; Ng, AP; Cory, S;
- Details
- Publication Year 2023-02-08,Volume 30,Issue #4,Page 1018-1032
- Journal Title
- Cell Death & Differentiation
- Abstract
- The importance of c-MYC in regulating lymphopoiesis and promoting lymphomagenesis is well-established. Far less appreciated is the vital supporting role of MYC's relative MNT. Using Rag1Cre-mediated Mnt deletion in lymphoid progenitor cells, we show here that, during normal T cell development, MNT loss enhances apoptosis, at least in part by elevating expression of the pro-apoptotic BH3-only protein BIM. Moreover, using T lymphoma-prone VavP-MYC transgenic mice, we show that Mnt deletion reduces the pool of pre-malignant MYC-driven T lymphoid cells and abrogates thymic T lymphomagenesis. In addition, we establish that Mnt deletion prevents T lymphoma development in γ-irradiated mice, most likely by enhancing apoptosis of T lymphoid cells repopulating the depleted thymus. Taken together with our recent demonstration that MNT is vital for the survival of MYC-driven pre-malignant and malignant B lymphoid cells, these results suggest that MNT represents an important new drug target for both T and B lymphoid malignancies.
- Publisher
- NPG
- Research Division(s)
- Blood Cells And Blood Cancer
- PubMed ID
- 36755068
- Publisher's Version
- https://doi.org/10.1038/s41418-023-01119-y
- Open Access at Publisher's Site
https://doi.org/10.1038/s41418-023-01119-y.- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-03-17 11:09:13
Last Modified: 2023-04-12 09:54:50