| Aberrant DNA hypermethylation signature in acute myeloid leukemia directed by EVI1. | |
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MedLine Citation:
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PMID: 20855866 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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DNA methylation patterns are frequently dysregulated in cancer, although little is known of the mechanisms through which specific gene sets become aberrantly methylated. The ecotropic viral integration site 1 (EVI1) locus encodes a DNA binding zinc-finger transcription factor that is aberrantly expressed in a subset of acute myeloid leukemia (AML) patients with poor outcome. We find that the promoter DNA methylation signature of EVI1 AML blast cells differs from those of normal CD34(+) bone marrow cells and other AMLs. This signature contained 294 differentially methylated genes, of which 238 (81%) were coordinately hypermethylated. An unbiased motif analysis revealed an overrepresentation of EVI1 binding sites among these aberrantly hypermethylated loci. EVI1 was capable of binding to these promoters in 2 different EVI1-expressing cell lines, whereas no binding was observed in an EVI1-negative cell line. Furthermore, EVI1 was observed to interact with DNA methyl transferases 3A and 3B. Among the EVI1 AML cases, 2 subgroups were recognized, of which 1 contained AMLs with many more methylated genes, which was associated with significantly higher levels of EVI1 than in the cases of the other subgroup. Our data point to a role for EVI1 in directing aberrant promoter DNA methylation patterning in EVI1 AMLs. |
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Authors:
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Sanne Lugthart; Maria E Figueroa; Eric Bindels; Lucy Skrabanek; Peter J M Valk; Yushan Li; Stefan Meyer; Claudia Erpelinck-Verschueren; John Greally; Bob Löwenberg; Ari Melnick; Ruud Delwel |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-20 |
Journal Detail:
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Title: Blood Volume: 117 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-07 Completed Date: 2011-02-24 Revised Date: 2012-01-06 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 234-41 Citation Subset: AIM; IM |
Affiliation:
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Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Blotting, Western Chromatin Immunoprecipitation DNA (Cytosine-5-)-Methyltransferase / genetics, metabolism DNA Methylation* DNA, Neoplasm / genetics DNA-Binding Proteins / genetics*, metabolism Female Humans Leukemia, Myeloid, Acute / genetics*, metabolism, pathology Male Middle Aged Polymerase Chain Reaction Promoter Regions, Genetic / genetics* Proto-Oncogenes / genetics* Transcription Factors / genetics*, metabolism Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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GM007288/GM/NIGMS NIH HHS; R8301-HD044078/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/DNA-Binding Proteins; 0/MECOM protein, human; 0/Transcription Factors; EC 2.1.1.37/DNA (Cytosine-5-)-Methyltransferase; EC 2.1.1.37/DNA methyltransferase 3A; EC 2.1.1.37/DNA methyltransferase 3B |
| Comments/Corrections | |
Comment In:
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Blood. 2011 Jan 6;117(1):4-5
[PMID:
21212288
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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