Loss of a single Mcl-1 allele inhibits MYC-driven lymphomagenesis by sensitizing Pro-B cells to apoptosis
- Author(s)
- Grabow, S; Delbridge, AR; Aubrey, BJ; Vandenberg, CJ; Strasser, A;
- Details
- Publication Year 2016-03-15,Volume 14,Issue #10,Page 2337-47
- Journal Title
- Cell Rep
- Publication Type
- Journal Article
- Abstract
- MCL-1 is critical for progenitor cell survival during emergency hematopoiesis, but its role in sustaining cells undergoing transformation and in lymphomagenesis is only poorly understood. We investigated the importance of MCL-1 in the survival of B lymphoid progenitors undergoing MYC-driven transformation and its functional interactions with pro-apoptotic BIM and PUMA and the tumor suppressor p53 in lymphoma development. Loss of one Mcl-1 allele almost abrogated MYC-driven-lymphoma development owing to a reduction in lymphoma initiating pre-B cells. Although loss of the p53 target PUMA had minor impact, loss of one p53 allele substantially accelerated lymphoma development when MCL-1 was limiting, most likely because p53 loss also causes defects in non-apoptotic tumor suppressive processes. Remarkably, loss of BIM restored the survival of lymphoma initiating cells and rate of tumor development. Thus, MCL-1 has a major role in lymphoma initiating pro-B cells to oppose BIM, which is upregulated in response to oncogenic stress.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 26947081
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2016.02.039
- Open Access at Publisher's Site
http://www.sciencedirect.com/science/article/pii/S2211124716301425- NHMRC Grants
- NHMRC/1020363,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-03-15 03:47:43
Last Modified: 2016-05-09 12:34:25