Details

Autor(en) / Beteiligte

• Kelly, Gemma L
• Grabow, Stephanie
• Glaser, Stefan P
• Fitzsimmons, Leah
• Aubrey, Brandon J
• Okamoto, Toru
• Valente, Liz J
• Robati, Mikara
• Tai, Lin
• Fairlie, W Douglas
• Lee, Erinna F
• Lindstrom, Mikael S
• Wiman, Klas G
• Huang, David C S
• Bouillet, Philippe
• Rowe, Martin
• Rickinson, Alan B
• Herold, Marco J
• Strasser, Andreas

Titel

Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53

Ist Teil von

• Genes & development, 2014-01, Vol.28 (1), p.58-70

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.