Critical B-lymphoid cell intrinsic role of endogenous MCL-1 in c-MYC-induced lymphomagenesis
- Author(s)
- Grabow, S; Kelly, GL; Delbridge, AR; Kelly, PN; Bouillet, P; Adams, JM; Strasser, A;
- Journal Title
- Cell Death Dis
- Publication Type
- Journal Article
- Abstract
- Evasion of apoptosis is critical for tumorigenesis, and sustained survival of nascent neoplastic cells may depend upon the endogenous levels of pro-survival BCL-2 family members. Indeed, previous studies using gene-targeted mice revealed that BCL-XL, but surprisingly not BCL-2, is critical for the development of c-MYC-induced pre-B/B lymphomas. However, it remains unclear whether another pro-survival BCL-2 relative contributes to their development. MCL-1 is an intriguing candidate, because it is required for cell survival during early B-lymphocyte differentiation. It is expressed abnormally high in several types of human B-cell lymphomas and is implicated in their resistance to chemotherapy. To test the B-cell intrinsic requirement for endogenous MCL-1 in lymphoma development, we conditionally deleted Mcl-1 in B-lymphoid cells of Emu-Myc transgenic mice. We found that MCL-1 loss in early B-lymphoid progenitors delayed MYC-driven lymphomagenesis. Moreover, the lymphomas that arose when MCL-1 levels were diminished appeared to have been selected for reduced levels of BIM and/or increased levels of BCL-XL. These results underscore the importance of MCL-1 in lymphoma development and show that alterations in the levels of other cell death regulators can compensate for deficiencies in MCL-1 expression.
- Publisher
- NPG
- Research Division(s)
- Molecular Genetics Of Cancer
- PubMed ID
- 26962682
- Publisher's Version
- https://doi.org/10.1038/cddis.2016.43
- Open Access at Publisher's Site
http://www.nature.com/cddis/journal/v7/n3/full/cddis201643a.html- NHMRC Grants
- NHMRC/1016701, NHMRC/1020363,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-03-15 03:47:43
Last Modified: 2016-03-15 03:57:12