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rdf:type |
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lifeskim:mentions |
umls-concept:C0007589,
umls-concept:C0026882,
umls-concept:C0031437,
umls-concept:C0229601,
umls-concept:C0542341,
umls-concept:C1274040,
umls-concept:C1415876,
umls-concept:C1415877,
umls-concept:C1511938,
umls-concept:C1512554,
umls-concept:C1825692
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pubmed:issue |
6
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pubmed:dateCreated |
2010-12-15
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pubmed:abstractText |
Cancer-associated IDH mutations are characterized by neomorphic enzyme activity and resultant 2-hydroxyglutarate (2HG) production. Mutational and epigenetic profiling of a large acute myeloid leukemia (AML) patient cohort revealed that IDH1/2-mutant AMLs display global DNA hypermethylation and a specific hypermethylation signature. Furthermore, expression of 2HG-producing IDH alleles in cells induced global DNA hypermethylation. In the AML cohort, IDH1/2 mutations were mutually exclusive with mutations in the ?-ketoglutarate-dependent enzyme TET2, and TET2 loss-of-function mutations were associated with similar epigenetic defects as IDH1/2 mutants. Consistent with these genetic and epigenetic data, expression of IDH mutants impaired TET2 catalytic function in cells. Finally, either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic differentiation and increased stem/progenitor cell marker expression, suggesting a shared proleukemogenic effect.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5-Methylcytosine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IDH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Isocitrate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/MECOM protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TET2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/isocitrate dehydrogenase 2, human
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1878-3686
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pubmed:author |
pubmed-author:Abdel-WahabOmarO,
pubmed-author:BhagwatNehaN,
pubmed-author:ChoeSung ESE,
pubmed-author:DelwelRuudR,
pubmed-author:FantinValeria RVR,
pubmed-author:FernandezHugo FHF,
pubmed-author:FigueroaMaria EME,
pubmed-author:GodleyLucy ALA,
pubmed-author:LöwenbergBobB,
pubmed-author:LevineRoss LRL,
pubmed-author:LiYushanY,
pubmed-author:LichtJonathan DJD,
pubmed-author:LuChaoC,
pubmed-author:MelnickAriA,
pubmed-author:PaiettaElisabethE,
pubmed-author:ParksS NSN,
pubmed-author:PeetersJustine KJK,
pubmed-author:ShihAlanA,
pubmed-author:SunZhuoxinZ,
pubmed-author:TallmanMartin SMS,
pubmed-author:ThompsonCraig BCB,
pubmed-author:TomP APA,
pubmed-author:ValkPeter J MPJ,
pubmed-author:VasanthakumarAparnaA,
pubmed-author:WardPatrick SPS,
pubmed-author:WolniakKristyK
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
553-67
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pubmed:meshHeading |
pubmed-meshheading:21130701-5-Methylcytosine,
pubmed-meshheading:21130701-Cell Differentiation,
pubmed-meshheading:21130701-DNA Methylation,
pubmed-meshheading:21130701-DNA-Binding Proteins,
pubmed-meshheading:21130701-GATA1 Transcription Factor,
pubmed-meshheading:21130701-Gene Regulatory Networks,
pubmed-meshheading:21130701-Humans,
pubmed-meshheading:21130701-Hydroxylation,
pubmed-meshheading:21130701-Isocitrate Dehydrogenase,
pubmed-meshheading:21130701-Leukemia, Myeloid, Acute,
pubmed-meshheading:21130701-Mutation,
pubmed-meshheading:21130701-Myeloid Cells,
pubmed-meshheading:21130701-Phenotype,
pubmed-meshheading:21130701-Proto-Oncogene Proteins,
pubmed-meshheading:21130701-Proto-Oncogenes,
pubmed-meshheading:21130701-Transcription Factors
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pubmed:year |
2010
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pubmed:articleTitle |
Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation.
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pubmed:affiliation |
Weill Cornell Medical College, New York, NY 10065, USA.
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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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