Title |
Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53
|
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Published in |
Genes & Development, January 2014
|
DOI | 10.1101/gad.232009.113 |
Pubmed ID | |
Authors |
Gemma L. Kelly, Stephanie Grabow, Stefan P. Glaser, Leah Fitzsimmons, Brandon J. Aubrey, Toru Okamoto, Liz J. Valente, Mikara Robati, Lin Tai, W. Douglas Fairlie, Erinna F. Lee, Mikael S. Lindstrom, Klas G. Wiman, David C.S. Huang, Philippe Bouillet, Martin Rowe, Alan B. Rickinson, Marco J. Herold, Andreas Strasser |
Abstract |
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. |
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Demographic breakdown
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Scientists | 1 | 100% |
Mendeley readers
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Malaysia | 1 | <1% |
United Kingdom | 1 | <1% |
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Unknown | 101 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 25 | 24% |
Student > Bachelor | 8 | 8% |
Student > Doctoral Student | 7 | 7% |
Other | 7 | 7% |
Other | 15 | 14% |
Unknown | 18 | 17% |
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Biochemistry, Genetics and Molecular Biology | 21 | 20% |
Medicine and Dentistry | 14 | 13% |
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Immunology and Microbiology | 5 | 5% |
Other | 3 | 3% |
Unknown | 19 | 18% |