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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 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 Citation Map 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. Related Collections Neoplasia Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief Report DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia Annegret Glasow1,2, Angela Barrett1, Kevin Petrie1, Rajeev Gupta3, Manuel Boix-Chornet1, Da-Cheng Zhou4, David Grimwade5, Robert Gallagher4, Marieke von Lindern6, Samuel Waxman7, Tariq Enver3, Guido Hildebrandt2, and Arthur Zelent1 1 Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom; 2 Department of Radiotherapy and Radio-oncology, University of Leipzig, Leipzig, Germany; 3 Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; 4 Department of Oncology and Pathology, Albert Einstein Cancer Center, New York, NY; 5 Department of Medical and Molecular Genetics, King's College, London, United Kingdom; 6 Department of Hematology, Erasmus Medical Centre, Rotterdam, the Netherlands; and 7 Department of Medicine, Mount Sinai School of Medicine, New York, NY The retinoic acid receptor (RAR) gene (RARA) encodes 2 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 down-regulated 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?

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