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, Arthur Zelent

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2374-2377
Number of pages4
JournalBlood
Volume111
Issue number4
DOIs
StatePublished - Feb 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Glasow, A., Barrett, A., Petrie, K., Gupta, R., Boix-Chornet, M., Zhou, D. C., Grimwade, D., Gallagher, R., Von Lindern, M., Waxman, S., Enver, T., Hildebrandt, G., & Zelent, A. (2008). DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia. Blood, 111(4), 2374-2377. https://doi.org/10.1182/blood-2007-05-088344