Endogenous Bcl-x(L) is essential for Myc-driven lymphomagenesis in mice
Details
Publication Year 2011-12-08,Volume 118,Issue #24,Page 6380-6386
Journal Title
BLOOD
Publication Type
Journal Article
Abstract
Impaired apoptosis is a cancer hallmark, and some types of lymphomas and other cancers harbor mutations that directly affect key cell death regulators, such as Bcl-2 family members. However, because the majority of tumors seem to lack such mutations, we are examining the hypothesis that tumorigenesis can be sustained at least initially by the normal expression of specific endogenous pro-survival Bcl-2 family members. We previously demonstrated that the lymphomagenesis in E mu-myc transgenic mice, which constitutively overexpress the c-Myc oncoprotein in B-lymphoid cells and develop pre-B and B-cell lymphomas, does not require endogenous Bcl-2. In striking contrast, we report here that loss in these mice of its close relative Bcl-x(L) attenuated the pre-neoplastic expansion of pro-B and pre-B cells otherwise driven by c-Myc overexpression, sensitized these cells to apoptosis and ablated lymphoma formation. Remarkably, even loss of a single bcl-x allele delayed the lymphomagenesis. These findings identify Bcl-x(L) as a prerequisite for the emergence of c-Myc-driven pre-B/B lymphoma and suggest that BH3 mimetic drugs may provide a prophylactic strategy for c-Myc-driven tumors. (Blood. 2011;118(24):6380-6386)
Publisher
AMER SOC HEMATOLOGY
Keywords
APOPTOTIC CELL-DEATH; C-MYC; TRANSGENIC MICE; B-CELLS; BH3-ONLY PROTEINS; PRE-B; BCL-2; FAMILY; PUMA; LEUKEMIA
Research Division(s)
Molecular Genetics Of Cancer
Terms of Use/Rights Notice
Copyright © 2011 by The American Society of Hematology


Creation Date: 2011-12-08 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙