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

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, Agustin Chicas, James C. Mulloy, Scott C. Kogan, Patrick Brown, Peter Valent, James E. Bradner, Scott W. Lowe () and Christopher R. Vakoc ()
Additional contact information
Johannes Zuber: Cold Spring Harbor Laboratory, 1 Bungtown Road
Junwei Shi: Cold Spring Harbor Laboratory, 1 Bungtown Road
Eric Wang: Cold Spring Harbor Laboratory, 1 Bungtown Road
Amy R. Rappaport: Cold Spring Harbor Laboratory, 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
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
Christopher R. Vakoc: Cold Spring Harbor Laboratory, 1 Bungtown Road

Nature, 2011, vol. 478, issue 7370, 524-528

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.

Date: 2011
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DOI: 10.1038/nature10334

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