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Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

Author

Listed:
  • Mark A. Dawson

    (Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge
    Gurdon Institute and Department of Pathology)

  • Rab K. Prinjha

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Antje Dittmann

    (Cellzome AG Meyerhofstrasse 1)

  • George Giotopoulos

    (Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge)

  • Marcus Bantscheff

    (Cellzome AG Meyerhofstrasse 1)

  • Wai-In Chan

    (Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge)

  • Samuel C. Robson

    (Gurdon Institute and Department of Pathology)

  • Chun-wa Chung

    (Molecular Discovery Research, GlaxoSmithKline R&D)

  • Carsten Hopf

    (Cellzome AG Meyerhofstrasse 1)

  • Mikhail M. Savitski

    (Cellzome AG Meyerhofstrasse 1)

  • Carola Huthmacher

    (Cellzome AG Meyerhofstrasse 1)

  • Emma Gudgin

    (Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge)

  • Dave Lugo

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Soren Beinke

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Trevor D. Chapman

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Emma J. Roberts

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Peter E. Soden

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Kurt R. Auger

    (Cancer Epigenetics DPU, Oncology R&D, GlaxoSmithKline, 1250 South Collegeville Road)

  • Olivier Mirguet

    (Lipid Metabolism Discovery Performance Unit, GSK R&D)

  • Konstanze Doehner

    (University Hospital of Ulm Internal Medicine III Albert- Einstein-Allee 23)

  • Ruud Delwel

    (Erasmus University Medical Center)

  • Alan K. Burnett

    (Cardiff University School of Medicine)

  • Phillip Jeffrey

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre)

  • Gerard Drewes

    (Cellzome AG Meyerhofstrasse 1)

  • Kevin Lee

    (Epinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre
    I-BET151 compound requests should be directed to K.L. (Kevin.2.lee@gsk.com))

  • Brian J. P. Huntly

    (Cambridge Institute for Medical Research and Addenbrookes Hospital, University of Cambridge)

  • Tony Kouzarides

    (Gurdon Institute and Department of Pathology)

Abstract

BET proteins as targets in mixed lineage leukaemia Rearrangements of the MLL (mixed lineage leukaemia) gene, and chimaeric MLL-fusion proteins, occur in a number of aggressive leukaemias including acute myeloid leukemia (AML). Tony Kouzarides and colleagues now find that MLL-fusion proteins are associated with BET family proteins in transcription factor complexes. GSK1210151A (I-BET151), a new small-molecule inhibitor of the interaction between BET family proteins and specific chromatin marks, is shown to have efficacy against AML cells in vitro and in mouse models, suggesting a new therapeutic strategy for AML.

Suggested Citation

  • Mark A. Dawson & Rab K. Prinjha & Antje Dittmann & George Giotopoulos & Marcus Bantscheff & Wai-In Chan & Samuel C. Robson & Chun-wa Chung & Carsten Hopf & Mikhail M. Savitski & Carola Huthmacher & Em, 2011. "Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia," Nature, Nature, vol. 478(7370), pages 529-533, October.
    • Handle: RePEc:nat:nature:v:478:y:2011:i:7370:d:10.1038_nature10509
    DOI: 10.1038/nature10509
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    Cited by:

    1. Irene Robles-Rebollo & Sergi Cuartero & Adria Canellas-Socias & Sarah Wells & Mohammad M. Karimi & Elisabetta Mereu & Alexandra G. Chivu & Holger Heyn & Chad Whilding & Dirk Dormann & Samuel Marguerat, 2022. "Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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