Targeting of MCL-1 kills MYC-driven mouse and human lymphoma cells even when they bear mutations in p53
Publication Year 2014-01-01, Volume 28, Issue #1, Page 58-70
Journal Title
Genes Dev
Publication Type
Journal Article
The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers
cancer ; apoptosis ; MCL-1 ; p53 ; BCL-2 ; MYC
WEHI Research Division(s)
Molecular Genetics Of Cancer; Cancer And Haematology; Chemical Biology; Structural Biology
Rights Notice
© 2014 Kelly et al.; Published by Cold Spring Harbor Laboratory Press This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at

Creation Date: 2014-01-14 03:36:32
Last Modified: 0001-01-01 12:00:00
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