IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v391y1998i6669d10.1038_35895.html
   My bibliography  Save this article

Role of the histone deacetylase complex in acute promyelocytic leukaemia

Author

Listed:
  • Richard J. Lin

    (Howard Hughes Medical Institute
    The Salk Institute for Biological Studies
    Graduate Program in Molecular Pathology, University of California San Diego, School of Medicine)

  • Laszlo Nagy

    (Howard Hughes Medical Institute
    The Salk Institute for Biological Studies)

  • Satoshi Inoue

    (The Salk Institute for Biological Studies)

  • Wenlin Shao

    (Lady Davis Institute for Medical Research)

  • Wilson H. Miller

    (Lady Davis Institute for Medical Research)

  • Ronald M. Evans

    (Howard Hughes Medical Institute
    The Salk Institute for Biological Studies)

Abstract

Non-liganded retinoic acid receptors (RARs) repress transcription of target genes by recruiting the histone deacetylase complex1,2,3 through a class of silencing mediators termed SMRT or N-CoR4,5. Mutant forms of RARα, created by chromosomal translocations with either the PML (for promyelocytic leukaemia)6,7,8 or the PLZF (for promyelocytic leukaemia zinc finger)9,10 locus, are oncogenic and result in human acute promyelocytic leukaemia (APL). PML–RARα APL patients achieve complete remission following treatments with pharmacological doses of retinoic acids (RA); in contrast, PLZF–RARα patients respond very poorly, if at all11. Here we report that the association of these two chimaeric receptors with the histone deacetylase (HDAC) complex helps to determine both the development of APL and the ability of patients to respond to retinoids. Consistent with these observations, inhibitors of histone deacetylase dramatically potentiate retinoid-induced differentiation of RA-sensitive, and restore retinoid responses of RA-resistant, APL cell lines. Our findings suggest that oncogenic RARs mediate leukaemogenesis through aberrant chromatin acetylation, and that pharmacological manipulation of nuclear receptor co-factors may be a useful approach in the treatment of human disease.

Suggested Citation

  • Richard J. Lin & Laszlo Nagy & Satoshi Inoue & Wenlin Shao & Wilson H. Miller & Ronald M. Evans, 1998. "Role of the histone deacetylase complex in acute promyelocytic leukaemia," Nature, Nature, vol. 391(6669), pages 811-814, February.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6669:d:10.1038_35895
    DOI: 10.1038/35895
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35895
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/35895?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. William Villiers & Audrey Kelly & Xiaohan He & James Kaufman-Cook & Abdurrahman Elbasir & Halima Bensmail & Paul Lavender & Richard Dillon & Borbála Mifsud & Cameron S. Osborne, 2023. "Multi-omics and machine learning reveal context-specific gene regulatory activities of PML::RARA in acute promyelocytic leukemia," Nature Communications, Nature, vol. 14(1), pages 1-17, 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:391:y:1998:i:6669:d:10.1038_35895. 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.