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RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

Author

Listed:
  • Johannes Zuber

    (Cold Spring Harbor Laboratory, 1 Bungtown Road
    Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria)

  • Junwei Shi

    (Cold Spring Harbor Laboratory, 1 Bungtown Road
    Molecular and Cellular Biology Program, Stony Brook University)

  • Eric Wang

    (Cold Spring Harbor Laboratory, 1 Bungtown Road)

  • Amy R. Rappaport

    (Cold Spring Harbor Laboratory, 1 Bungtown Road
    Watson School of Biological Sciences, 1 Bungtown Road)

  • Harald Herrmann

    (Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, A-1090 Vienna, Austria)

  • Edward A. Sison

    (Johns Hopkins University School of Medicine)

  • Daniel Magoon

    (Johns Hopkins University School of Medicine)

  • Jun Qi

    (Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Katharina Blatt

    (Medical University of Vienna, A-1090 Vienna, Austria)

  • Mark Wunderlich

    (Cincinnati Children’s Hospital Medical Center)

  • Meredith J. Taylor

    (Cold Spring Harbor Laboratory, 1 Bungtown Road)

  • Christopher Johns

    (Cold Spring Harbor Laboratory, 1 Bungtown Road)

  • Agustin Chicas

    (Cold Spring Harbor Laboratory, 1 Bungtown Road)

  • James C. Mulloy

    (Cincinnati Children’s Hospital Medical Center)

  • Scott C. Kogan

    (University of California at San Francisco)

  • Patrick Brown

    (Johns Hopkins University School of Medicine)

  • Peter Valent

    (Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, A-1090 Vienna, Austria
    Medical University of Vienna, A-1090 Vienna, Austria)

  • James E. Bradner

    (Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Scott W. Lowe

    (Cold Spring Harbor Laboratory, 1 Bungtown Road
    Watson School of Biological Sciences, 1 Bungtown Road
    Howard Hughes Medical Institute, 1 Bungtown Road)

  • Christopher R. Vakoc

    (Cold Spring Harbor Laboratory, 1 Bungtown Road)

Abstract

Brd4 target in acute myeloid leukaemia In an RNAi screen targeting chromatin regulators, Vakoc and colleagues find that maintenance of acute myeloid leukaemia (AML) requires Brd4, which binds to acetylated histones to influence gene transcription. Brd4 regulates expression of the oncogene Myc and a Myc-driven gene-expression program that permits leukaemia cells to self-renew. JQ1, a small molecule that inhibits Brd4 function, has anti-leukaemic effects in a mouse model and inhibits the proliferation of primary human AML cells, suggesting a therapeutic approach in patients with AML.

Suggested Citation

  • Johannes Zuber & Junwei Shi & Eric Wang & Amy R. Rappaport & Harald Herrmann & Edward A. Sison & Daniel Magoon & Jun Qi & Katharina Blatt & Mark Wunderlich & Meredith J. Taylor & Christopher Johns & A, 2011. "RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia," Nature, Nature, vol. 478(7370), pages 524-528, October.
    • Handle: RePEc:nat:nature:v:478:y:2011:i:7370:d:10.1038_nature10334
    DOI: 10.1038/nature10334
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    Cited by:

    1. Stella Amanda & Tze King Tan & Jolynn Zu Lin Ong & Madelaine Skolastika Theardy & Regina Wan Ju Wong & Xiao Zi Huang & Muhammad Zulfaqar Ali & Yan Li & Zhiyuan Gong & Hiroshi Inagaki & Ee Yong Foo & B, 2022. "IRF4 drives clonal evolution and lineage choice in a zebrafish model of T-cell lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Yansheng Zhai & Xiaoyan Huang & Keren Zhang & Yuchen Huang & Yanlong Jiang & Jingwei Cui & Zhe Zhang & Cookson K. C. Chiu & Weiye Zhong & Gang Li, 2022. "Spatiotemporal-resolved protein networks profiling with photoactivation dependent proximity labeling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Edurne San José-Enériz & Naroa Gimenez-Camino & Obdulia Rabal & Leire Garate & Estibaliz Miranda & Nahia Gómez-Echarte & Fernando García & Stella Charalampopoulou & Elena Sáez & Amaia Vilas-Zornoza & , 2024. "Epigenetic-based differentiation therapy for Acute Myeloid Leukemia," Nature Communications, Nature, vol. 15(1), pages 1-23, December.

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