SEARCH:   Advanced

Blood, 15 February 2008, Vol. 111, No. 4, pp. 2374-2377. Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-05-088344. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-088344v1 111/4/2374    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Glasow, A. Articles by Zelent, A. Search for Related Content PubMed PubMed Citation Articles by Glasow, A. Articles by Zelent, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 7, 2007 Accepted October 28, 2007 DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia Annegret Glasow, Angela Barrett, Kevin Petrie, Rajeev Gupta, Manuel Boix-Chornet, Da-Cheng Zhou, David Grimwade, Robert Gallagher, Marieke von Lindern, Samuel Waxman, Tariq Enver, Guido Hildebrandt, and Arthur Zelent* Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicien, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom Department of Oncology and Pathology, Albert Einstein Cancer Centre, New York, NY, United States Department of Medical and Molecular Genetics, King's College, London, United Kingdom Department of Hematology, Erasmus Medical Centre, Rotterdam, Netherlands Department of Medicine, Mount Sinai School of Medicine, New York, NY, United States Department of Radiotherapy and Radio-oncology, University of Leipzig, Leipzig, Germany * Corresponding author; email: arthur.zelent{at}icr.ac.uk. Retinoic acid receptor (RARA) encodes two major isoforms and mediates positive effects of all-trans-retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RAR2) isoform increases with myelomonocytic differentiation and appears to be downregulated in many acute myeloid leukemia (AML) cell lines. Here we demonstrate that relative to normal myeloid stem/progenitor cells, RAR2 expression is dramatically reduced in primary AML blasts. Expression of the RAR1 isoform is also significantly reduced in primary AML cells, but not in AML cell lines. Although the promoters directing expression of RAR1 and RAR2 are respectively unmethylated and methylated in AML cell lines, these regulatory regions are unmethylated in all the AML patient cell samples analyzed. Moreover, in primary AML cells histones associated with the RAR2 promoter possessed diminished levels of H3 acetylation and lysine 4 methylation. These results underscore the complexities of the mechanisms responsible for deregulation of gene expression in AML and support the notion that diminished RARA expression contributes to leukemogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020