BET inhibitor resistance emerges from leukaemia stem cells

Chun Yew Fong, Omer Gilan, Enid Y. N. Lam, Alan F. Rubin, Sarah Ftouni, Dean Tyler, Kym Stanley, Devbarna Sinha, Paul Yeh, Jessica Morison, George Giotopoulos, Dave Lugo, Philip Jeffrey, Stanley Chun-Wei Lee, Christopher Carpenter, Richard Gregory, Robert G. Ramsay, Steven W. Lane, Omar Abdel-Wahab, Tony Kouzarides, Ricky W. Johnstone, Sarah-Jane Dawson, Brian J. P. Huntly, Rab K. Prinjha, Anthony T. Papenfuss and Mark A. Dawson ()
Additional contact information
Chun Yew Fong: Peter MacCallum Cancer Centre
Omer Gilan: Peter MacCallum Cancer Centre
Enid Y. N. Lam: Peter MacCallum Cancer Centre
Alan F. Rubin: The Walter & Eliza Hall Institute of Medical Research
Sarah Ftouni: Peter MacCallum Cancer Centre
Dean Tyler: Peter MacCallum Cancer Centre
Kym Stanley: Peter MacCallum Cancer Centre
Devbarna Sinha: Peter MacCallum Cancer Centre
Paul Yeh: Peter MacCallum Cancer Centre
Jessica Morison: Cambridge Institute for Medical Research and Wellcome Trust-MRC Stem Cell Institute
George Giotopoulos: Cambridge Institute for Medical Research and Wellcome Trust-MRC Stem Cell Institute
Dave Lugo: Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre
Philip Jeffrey: Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre
Stanley Chun-Wei Lee: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Christopher Carpenter: Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline
Richard Gregory: Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre
Robert G. Ramsay: Peter MacCallum Cancer Centre
Steven W. Lane: QIMR Berghofer Medical Research Institute, University of Queensland
Omar Abdel-Wahab: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Tony Kouzarides: Gurdon Institute and Department of Pathology
Ricky W. Johnstone: Peter MacCallum Cancer Centre
Sarah-Jane Dawson: Peter MacCallum Cancer Centre
Brian J. P. Huntly: Cambridge Institute for Medical Research and Wellcome Trust-MRC Stem Cell Institute
Rab K. Prinjha: Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre
Anthony T. Papenfuss: Peter MacCallum Cancer Centre
Mark A. Dawson: Peter MacCallum Cancer Centre

Nature, 2015, vol. 525, issue 7570, 538-542

Abstract: BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here, in a MLL–AF9 mouse leukaemia model, resistance to BET inhibitors is shown to emerge from leukaemia stem cells, and be partly due to increased Wnt/β-catenin signalling.

Date: 2015
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DOI: 10.1038/nature14888

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