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BET inhibitor resistance emerges from leukaemia stem cells

Author

Listed:
  • Chun Yew Fong

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

  • Omer Gilan

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Enid Y. N. Lam

    (Peter MacCallum Cancer Centre)

  • Alan F. Rubin

    (The Walter & Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Sarah Ftouni

    (Peter MacCallum Cancer Centre)

  • Dean Tyler

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • Kym Stanley

    (Peter MacCallum Cancer Centre)

  • Devbarna Sinha

    (Peter MacCallum Cancer Centre)

  • Paul Yeh

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    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
    The University of Melbourne)

  • 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
    The University of Melbourne)

  • Sarah-Jane Dawson

    (Peter MacCallum Cancer Centre
    The University of Melbourne)

  • 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
    The University of Melbourne
    The Walter & Eliza Hall Institute of Medical Research
    University of Melbourne)

  • Mark A. Dawson

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    Peter MacCallum Cancer Centre)

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.

Suggested Citation

  • 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 & , 2015. "BET inhibitor resistance emerges from leukaemia stem cells," Nature, Nature, vol. 525(7570), pages 538-542, September.
    • Handle: RePEc:nat:nature:v:525:y:2015:i:7570:d:10.1038_nature14888
    DOI: 10.1038/nature14888
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    Cited by:

    1. Di Yu & Yingying Liang & Claudia Kim & Anbalagan Jaganathan & Donglei Ji & Xinye Han & Xuelan Yang & Yanjie Jia & Ruirui Gu & Chunyu Wang & Qiang Zhang & Ka Lung Cheung & Ming-Ming Zhou & Lei Zeng, 2023. "Structural mechanism of BRD4-NUT and p300 bipartite interaction in propagating aberrant gene transcription in chromatin in NUT carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Keith Woodley & Laura S. Dillingh & George Giotopoulos & Pedro Madrigal & Kevin M. Rattigan & Céline Philippe & Vilma Dembitz & Aoife M. S. Magee & Ryan Asby & Louie N. van de Lagemaat & Christopher M, 2023. "Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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