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- Annegret Glasow
- Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom;
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- Angela Barrett
- Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom;
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- Kevin Petrie
- Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom;
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- Rajeev Gupta
- Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom;
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- Manuel Boix-Chornet
- Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom;
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- Da-Cheng Zhou
- Department of Oncology and Pathology, Albert Einstein Cancer Center, New York, NY;
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- David Grimwade
- Department of Medical and Molecular Genetics, King's College, London, United Kingdom;
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- Robert Gallagher
- Department of Oncology and Pathology, Albert Einstein Cancer Center, New York, NY;
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- Marieke von Lindern
- Department of Hematology, Erasmus Medical Centre, Rotterdam, the Netherlands; and
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- Samuel Waxman
- Department of Medicine, Mount Sinai School of Medicine, New York, NY
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- Tariq Enver
- Medical Research Council (MRC) Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom;
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- Guido Hildebrandt
- Department of Radiotherapy and Radio-oncology, University of Leipzig, Leipzig, Germany;
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- Arthur Zelent
- Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom;
抄録
<jats:p>The retinoic acid receptor (RAR) α gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARα2) 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, RARα2 expression is dramatically reduced in primary AML blasts. Expression of the RARα1 isoform is also significantly reduced in primary AML cells, but not in AML cell lines. Although the promoters directing expression of RARα1 and RARα2 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 RARα2 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.</jats:p>
収録刊行物
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- Blood
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Blood 111 (4), 2374-2377, 2008-02-15
American Society of Hematology
