Journal article
Development and survival of MYC-driven lymphomas require the MYC antagonist MNT to curb MYC-induced apoptosis
Vu Nguyen Hai, Cassandra J Vandenberg, Ashley P Ng, Mikara R Robati, Natasha S Anstee, Joel Rimes, Edwin D Hawkins, Suzanne Cory
BLOOD | AMER SOC HEMATOLOGY | Published : 2020
Abstract
Deregulated overexpression 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 synergizes with MYC by suppressing MYC-driven apoptosis, and that it does so primarily by reducing the level of pro-apoptotic BIM. In Eμ-Myc mice, which model the MYC/IGH chromosome translocation in Burkitt's lymphoma, homozygous Mnt deletion greatly reduced lymphoma incidence by enhancing apopt..
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Awarded by National Health andMedical Research Council
Awarded by Leukemia & Lymphoma Society (Specialized Center of Research)
Awarded by Leukemia and Lymphoma Society
Awarded by RD Wright Fellowship
Funding Acknowledgements
This work was supported by grants from the National Health andMedical Research Council (program grant 461221) (S.C.) and the Leukemia & Lymphoma Society (Specialized Center of Research) grant 7001-13 (S.C.), National Health andMedical Research Council project grantsGNT1060179 and GNT1122783 (A.P.N.), Leukemia and Lymphoma Society USA 655218, National Health and Medical Research Council APP1145442 and an RD Wright Fellowship APP1159488 (E.D.H.), an Australia Postgraduate Award (J.R.), philanthropic support to the Walter and Eliza Hall Institute, and operational infrastructure grants through the Australian Government Independent Research Institute Infrastructure Support Scheme and the Victorian Government Operational Infrastructure Support.