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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-1-26
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pubmed:abstractText |
T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced neoplastic transformation remain undefined. We report here that constitutively active Notch1 activates the NF-kappaB pathway transcriptionally and via the IkappaB kinase (IKK) complex, thereby causing increased expression of several well characterized target genes of NF-kappaB in bone marrow hematopoietic stem cells and progenitors. Our observations demonstrate that the NF-kappaB pathway is highly active in established human T-ALL and that inhibition of the pathway can efficiently restrict tumor growth both in vitro and in vivo. These findings identify NF-kappaB as one of the major mediators of Notch1-induced transformation and suggest that the NF-kappaB pathway is a potential target of future therapies of T-ALL.
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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/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8,
http://linkedlifedata.com/resource/pubmed/chemical/Boronic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Il2rg protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin Receptor Common gamma...,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NOTCH1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines,
http://linkedlifedata.com/resource/pubmed/chemical/Rag2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Notch1,
http://linkedlifedata.com/resource/pubmed/chemical/bortezomib
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:AifantisIannisI,
pubmed-author:AlegreMaria-LuisaML,
pubmed-author:BuonamiciSilviaS,
pubmed-author:FerrandoAdolfoA,
pubmed-author:KeeBarbara LBL,
pubmed-author:MacarounSamiS,
pubmed-author:MandalMalayM,
pubmed-author:MascarenhasJoaquinaJ,
pubmed-author:MengFanyongF,
pubmed-author:MieleLucioL,
pubmed-author:PalomeroTeresaT,
pubmed-author:SpauldingChristinaC,
pubmed-author:ThompsonBenjamínB,
pubmed-author:VilimasTomasT
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
70-7
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17173050-Animals,
pubmed-meshheading:17173050-Antigens, CD4,
pubmed-meshheading:17173050-Antigens, CD8,
pubmed-meshheading:17173050-Boronic Acids,
pubmed-meshheading:17173050-COS Cells,
pubmed-meshheading:17173050-Cell Line,
pubmed-meshheading:17173050-Cell Line, Tumor,
pubmed-meshheading:17173050-Cell Survival,
pubmed-meshheading:17173050-Cercopithecus aethiops,
pubmed-meshheading:17173050-DNA-Binding Proteins,
pubmed-meshheading:17173050-Gene Expression Profiling,
pubmed-meshheading:17173050-Green Fluorescent Proteins,
pubmed-meshheading:17173050-Humans,
pubmed-meshheading:17173050-Interleukin Receptor Common gamma Subunit,
pubmed-meshheading:17173050-Leukemia, Experimental,
pubmed-meshheading:17173050-Leukemia, T-Cell,
pubmed-meshheading:17173050-Mice,
pubmed-meshheading:17173050-Mice, Inbred C57BL,
pubmed-meshheading:17173050-Mice, Knockout,
pubmed-meshheading:17173050-Microscopy, Confocal,
pubmed-meshheading:17173050-Mutation,
pubmed-meshheading:17173050-NF-kappa B,
pubmed-meshheading:17173050-Pyrazines,
pubmed-meshheading:17173050-Receptor, Notch1,
pubmed-meshheading:17173050-Signal Transduction,
pubmed-meshheading:17173050-Survival Analysis
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pubmed:year |
2007
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pubmed:articleTitle |
Targeting the NF-kappaB signaling pathway in Notch1-induced T-cell leukemia.
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pubmed:affiliation |
Department of Medicine, Section of Rheumatology, University of Chicago, 5841 South Maryland Avenue Chicago, Illinois 60637, 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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