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. © 2014 Kelly et al.
CITATION STYLE
Kelly, G. L., Grabow, S., Glaser, S. P., Fitzsimmons, L., Aubrey, B. J., Okamoto, T., … Strasser, A. (2014). Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53. Genes and Development, 28(1), 58–70. https://doi.org/10.1101/gad.232009.113
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