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DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia.

Glasow, Annegret, Barrett, Angela, Petrie, Kevin, Gupta, Rajeev, Boix-Chornet, Manuel, Zhou, Da-Cheng, Grimwade, David, Gallagher, Robert, von Lindern, Marieke, Waxman, Samuel, Enver, Tariq, Hildebrandt, Guido and Zelent, Arthur (2008) DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia. Blood, 111 (4). pp. 2374-7. ISSN 0006-4971

Item Type: Article

Abstract

The retinoic acid receptor (RAR) alpha gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARalpha2) 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, RARalpha2 expression is dramatically reduced in primary AML blasts. Expression of the RARalpha1 isoform is also significantly reduced in primary AML cells, but not in AML cell lines. Although the promoters directing expression of RARalpha1 and RARalpha2 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 RARalpha2 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.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12427
Identification Number: https://doi.org/10.1182/blood-2007-05-088344
ISSN: 0006-4971
URI: http://sure.sunderland.ac.uk/id/eprint/12427
Official URL: https://ashpublications.org/blood/article/111/4/23...

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 11:20
Last Modified: 30 Sep 2020 10:48

Contributors

Author: Kevin Petrie ORCID iD
Author: Annegret Glasow
Author: Angela Barrett
Author: Rajeev Gupta
Author: Manuel Boix-Chornet
Author: Da-Cheng Zhou
Author: David Grimwade
Author: Robert Gallagher
Author: Marieke von Lindern
Author: Samuel Waxman
Author: Tariq Enver
Author: Guido Hildebrandt
Author: Arthur Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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