Targeting leukemia on the DOT (original) (raw)

Epigenetics

Nature Chemical Biology volume 7, pages 663–665 (2011)Cite this article

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A combination of chemical and genetic approaches has established a proof of concept in mouse models—with strong mechanistic underpinning—indicating that targeting the aberrantly recruited histone methyltransferase activity of DOT1L has therapeutic potential in aggressive leukemias driven by MLL fusion genes.

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Figure 1: The first-in-class SAM-competitive and selective histone methyl transferase inhibitor EPZ004777 targets DOT1L-mediated H3K79 methylation at key MLL fusion target genes, leading to therapeutic effects in mixed-lineage leukemia.

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Acknowledgements

The authors wish to acknowledge B. Matijssen for assistance with Figure 1b.

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Authors and Affiliations

  1. Division of Cancer Therapeutics, Jon Travers and Paul Workman are in the Signal Transduction and Molecular Pharmacology Team, Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, UK.,
    Jon Travers & Paul Workman
  2. Division of Cancer Therapeutics, Julian Blagg is in the Medicinal Chemistry Team, Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, Sutton, UK.,
    Julian Blagg

Authors

  1. Jon Travers
  2. Julian Blagg
  3. Paul Workman

Corresponding author

Correspondence toPaul Workman.

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Competing interests

P.W. and J.B. are employees of and J.T. is a student of the Institute of Cancer Research. P.W. is also associated with Chroma Therapeutics and Nextech Invest Ltd.

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Travers, J., Blagg, J. & Workman, P. Targeting leukemia on the DOT.Nat Chem Biol 7, 663–665 (2011). https://doi.org/10.1038/nchembio.661

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