IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v478y2011i7370d10.1038_nature10509.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature10509
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature10509?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Jiahui Du & Yili Liu & Jinrui Sun & Enhui Yao & Jingyi Xu & Xiaolin Wu & Ling Xu & Mingliang Zhou & Guangzheng Yang & Xinquan Jiang, 2024. "ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:478:y:2011:i:7370:d:10.1038_nature10509. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.