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rdf:type |
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lifeskim:mentions |
umls-concept:C0023448,
umls-concept:C0023449,
umls-concept:C0033414,
umls-concept:C0038250,
umls-concept:C0086222,
umls-concept:C0180683,
umls-concept:C0599295,
umls-concept:C0851285,
umls-concept:C1517806,
umls-concept:C1551083,
umls-concept:C1705733,
umls-concept:C1961102
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pubmed:issue |
26
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pubmed:dateCreated |
2011-7-1
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pubmed:abstractText |
The Ets-related gene (ERG) is an Ets-transcription factor required for normal blood stem cell development. ERG expression is down-regulated during early T-lymphopoiesis but maintained in T-acute lymphoblastic leukemia (T-ALL), where it is recognized as an independent risk factor for adverse outcome. However, it is unclear whether ERG is directly involved in the pathogenesis of T-ALL and how its expression is regulated. Here we demonstrate that transgenic expression of ERG causes T-ALL in mice and that its knockdown reduces the proliferation of human MOLT4 T-ALL cells. We further demonstrate that ERG expression in primary human T-ALL cells is mediated by the binding of other T-cell oncogenes SCL/TAL1, LMO2, and LYL1 in concert with ERG, FLI1, and GATA3 to the ERG +85 enhancer. This enhancer is not active in normal T cells but in transgenic mice targets expression to fetal liver c-kit(+) cells, adult bone marrow stem/progenitors and early CD4(-)CD8(-) double-negative thymic progenitors. Taken together, these data illustrate that ERG promotes T-ALL and that failure to extinguish activity of stem cell enhancers associated with regulatory transcription factors such as ERG can contribute to the development of leukemia.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ERG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/LIM Domain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/LMO2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/LYL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-vav,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/TAL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:BirgerYehuditY,
pubmed-author:ChandrakanthanVasheV,
pubmed-author:FosterSamS,
pubmed-author:GöttgensBertholdB,
pubmed-author:GronerYoramY,
pubmed-author:IzraeliShaiS,
pubmed-author:JonquieresGeorgG,
pubmed-author:KinstonSarah JSJ,
pubmed-author:KirschenbaumYaelY,
pubmed-author:KnezevicKathyK,
pubmed-author:LockRichardR,
pubmed-author:MacKenzieKaren LKL,
pubmed-author:OramS HelenSH,
pubmed-author:PimandaJohn EJE,
pubmed-author:SpensbergerDominikD,
pubmed-author:ThomsJulie A IJA,
pubmed-author:WongJason WJW
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pubmed:issnType |
Electronic
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pubmed:day |
30
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7079-89
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21536859-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21536859-Animals,
pubmed-meshheading:21536859-Base Sequence,
pubmed-meshheading:21536859-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:21536859-Cell Line, Tumor,
pubmed-meshheading:21536859-Cell Proliferation,
pubmed-meshheading:21536859-Cells, Cultured,
pubmed-meshheading:21536859-DNA-Binding Proteins,
pubmed-meshheading:21536859-Gene Expression Regulation, Leukemic,
pubmed-meshheading:21536859-Gene Knockdown Techniques,
pubmed-meshheading:21536859-Humans,
pubmed-meshheading:21536859-LIM Domain Proteins,
pubmed-meshheading:21536859-Metalloproteins,
pubmed-meshheading:21536859-Mice,
pubmed-meshheading:21536859-Mice, Transgenic,
pubmed-meshheading:21536859-Molecular Sequence Data,
pubmed-meshheading:21536859-Neoplasm Proteins,
pubmed-meshheading:21536859-Neoplasm Transplantation,
pubmed-meshheading:21536859-Precursor T-Cell Lymphoblastic Leukemia-Lymphoma,
pubmed-meshheading:21536859-Promoter Regions, Genetic,
pubmed-meshheading:21536859-Proto-Oncogene Proteins,
pubmed-meshheading:21536859-Proto-Oncogene Proteins c-vav,
pubmed-meshheading:21536859-RNA, Messenger,
pubmed-meshheading:21536859-Sequence Alignment,
pubmed-meshheading:21536859-Survival Analysis,
pubmed-meshheading:21536859-T-Lymphocytes,
pubmed-meshheading:21536859-Trans-Activators
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pubmed:year |
2011
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pubmed:articleTitle |
ERG promotes T-acute lymphoblastic leukemia and is transcriptionally regulated in leukemic cells by a stem cell enhancer.
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pubmed:affiliation |
Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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