TY  - JOUR
AU  - Grabow, S
AU  - Kelly, GL
AU  - Delbridge, ARD
AU  - Kelly, PN
AU  - Bouillet, P
AU  - Adams, JM
AU  - Strasser, A
Y2  - 2021/02/05
Y1  - 2016/03/01
SN  - 2041-4889
UR  - http://hdl.handle.net/11343/260233
AB  - 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 Eμ-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.
LA  - English
PB  - NATURE PUBLISHING GROUP
T1  - Critical B-lymphoid cell intrinsic role of endogenous MCL-1 in c-MYC-induced lymphomagenesis
DO  - 10.1038/cddis.2016.43
IS  - Cell Death and Disease
VL  - 7
IS  - 3
L1  - /bitstream/handle/11343/260233/PMC4823944.pdf?sequence=1&isAllowed=y
ER  -