Nature Communications (Jan 2021)
BRD4-mediated repression of p53 is a target for combination therapy in AML
- Anne-Louise Latif,
- Ashley Newcombe,
- Sha Li,
- Kathryn Gilroy,
- Neil A. Robertson,
- Xue Lei,
- Helen J. S. Stewart,
- John Cole,
- Maria Terradas Terradas,
- Loveena Rishi,
- Lynn McGarry,
- Claire McKeeve,
- Claire Reid,
- William Clark,
- Joana Campos,
- Kristina Kirschner,
- Andrew Davis,
- Jonathan Lopez,
- Jun-ichi Sakamaki,
- Jennifer P. Morton,
- Kevin M. Ryan,
- Stephen W. G. Tait,
- Sheela A. Abraham,
- Tessa Holyoake,
- Brian Higgins,
- Xu Huang,
- Karen Blyth,
- Mhairi Copland,
- Timothy J. T. Chevassut,
- Karen Keeshan,
- Peter D. Adams
Affiliations
- Anne-Louise Latif
- Institute of Cancer Sciences, University of Glasgow
- Ashley Newcombe
- Institute of Cancer Sciences, University of Glasgow
- Sha Li
- Sanford Burnham Prebys Medical Discovery Institute
- Kathryn Gilroy
- Institute of Cancer Sciences, University of Glasgow
- Neil A. Robertson
- Institute of Cancer Sciences, University of Glasgow
- Xue Lei
- Sanford Burnham Prebys Medical Discovery Institute
- Helen J. S. Stewart
- Brighton and Sussex Medical School, University of Sussex
- John Cole
- Institute of Cancer Sciences, University of Glasgow
- Maria Terradas Terradas
- Institute of Cancer Sciences, University of Glasgow
- Loveena Rishi
- Institute of Cancer Sciences, University of Glasgow
- Lynn McGarry
- Cancer Research UK Beatson Institute
- Claire McKeeve
- West of Scotland Genomics Services (Laboratories), Queen Elizabeth University Hospital
- Claire Reid
- Institute of Cancer Sciences, University of Glasgow
- William Clark
- Cancer Research UK Beatson Institute
- Joana Campos
- Paul O’Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow
- Kristina Kirschner
- Institute of Cancer Sciences, University of Glasgow
- Andrew Davis
- Sanford Burnham Prebys Medical Discovery Institute
- Jonathan Lopez
- Institute of Cancer Sciences, University of Glasgow
- Jun-ichi Sakamaki
- Cancer Research UK Beatson Institute
- Jennifer P. Morton
- Institute of Cancer Sciences, University of Glasgow
- Kevin M. Ryan
- Cancer Research UK Beatson Institute
- Stephen W. G. Tait
- Institute of Cancer Sciences, University of Glasgow
- Sheela A. Abraham
- Paul O’Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow
- Tessa Holyoake
- Paul O’Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow
- Brian Higgins
- Pharma Research and Early Development, Roche Innovation Center-New York
- Xu Huang
- Paul O’Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow
- Karen Blyth
- Institute of Cancer Sciences, University of Glasgow
- Mhairi Copland
- Paul O’Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow
- Timothy J. T. Chevassut
- Brighton and Sussex Medical School, University of Sussex
- Karen Keeshan
- Paul O’Gorman Leukemia Research Centre, Institute of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow
- Peter D. Adams
- Institute of Cancer Sciences, University of Glasgow
- DOI
- https://doi.org/10.1038/s41467-020-20378-8
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 16
Abstract
MDM2 and BET inhibitors have shown efficacy in AML treatment. Here, the authors show that the two compounds can synergize through both p53 protein stabilization and inhibition of BRD4-mediated repression of p53 target genes.
