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rdf:type |
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lifeskim:mentions |
umls-concept:C0007589,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0049241,
umls-concept:C0049308,
umls-concept:C0086418,
umls-concept:C0229601,
umls-concept:C0439836,
umls-concept:C0870134,
umls-concept:C1511938,
umls-concept:C1516960
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pubmed:issue |
9
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pubmed:dateCreated |
2011-9-2
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pubmed:abstractText |
TET2 converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA and is frequently mutated in myeloid malignancies, including myeloproliferative neoplasms. Here we show that the level of 5-hmC is decreased in granulocyte DNA from myeloproliferative neoplasm patients with TET2 mutations compared with granulocyte DNA from healthy patients. Inhibition of TET2 by RNA interference decreases 5-hmC levels in both human leukemia cell lines and cord blood CD34(+) cells. These results confirm the enzymatic function of TET2 in human hematopoietic cells. Knockdown of TET2 in cord blood CD34(+) cells skews progenitor differentiation toward the granulomonocytic lineage at the expense of lymphoid and erythroid lineages. In addition, by monitoring in vitro granulomonocytic development we found a decreased granulocytic differentiation and an increase in monocytic cells. Our results indicate that TET2 disruption affects 5-hmC levels in human myeloid cells and participates in the pathogenesis of myeloid malignancies through the disturbance of myeloid differentiation.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:AlmireCaroleC,
pubmed-author:BernardOlivier AOA,
pubmed-author:CarbonneBrunoB,
pubmed-author:CasadevallNicoleN,
pubmed-author:DelhommeauFrançoisF,
pubmed-author:DroinNathalieN,
pubmed-author:GodleyLucy ALA,
pubmed-author:LargheroJérômeJ,
pubmed-author:Le CouédicJean-PierreJP,
pubmed-author:MasséAlineA,
pubmed-author:MokraniHayatH,
pubmed-author:PendinoFrédéricF,
pubmed-author:PloIsabelleI,
pubmed-author:PronierElodieE,
pubmed-author:RavanatJean-LucJL,
pubmed-author:SimonAudreyA,
pubmed-author:SolaryEricE,
pubmed-author:VainchenkerWilliamW,
pubmed-author:VasanthakumarAparnaA,
pubmed-author:da Costa Reis Monte MorBarbaraB
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2551-5
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pubmed:meshHeading |
pubmed-meshheading:21734233-5-Methylcytosine,
pubmed-meshheading:21734233-Cell Line, Tumor,
pubmed-meshheading:21734233-Cell Lineage,
pubmed-meshheading:21734233-Colony-Forming Units Assay,
pubmed-meshheading:21734233-Cytosine,
pubmed-meshheading:21734233-DNA Methylation,
pubmed-meshheading:21734233-DNA-Binding Proteins,
pubmed-meshheading:21734233-Erythropoiesis,
pubmed-meshheading:21734233-Fetal Blood,
pubmed-meshheading:21734233-Genetic Vectors,
pubmed-meshheading:21734233-Granulocytes,
pubmed-meshheading:21734233-Hematopoietic Stem Cells,
pubmed-meshheading:21734233-Humans,
pubmed-meshheading:21734233-Lentivirus,
pubmed-meshheading:21734233-Monocytes,
pubmed-meshheading:21734233-Mutation,
pubmed-meshheading:21734233-Myelopoiesis,
pubmed-meshheading:21734233-Proto-Oncogene Proteins,
pubmed-meshheading:21734233-RNA, Small Interfering,
pubmed-meshheading:21734233-RNA Interference
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pubmed:year |
2011
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pubmed:articleTitle |
Inhibition of TET2-mediated conversion of 5-methylcytosine to 5-hydroxymethylcytosine disturbs erythroid and granulomonocytic differentiation of human hematopoietic progenitors.
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pubmed:affiliation |
Inserm, U1009, Institut Gustave Roussy, Villejuif, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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