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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7346
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pubmed:dateCreated |
2011-5-12
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pubmed:databankReference |
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pubmed:abstractText |
Notch signalling is a central regulator of differentiation in a variety of organisms and tissue types. Its activity is controlled by the multi-subunit ?-secretase (?SE) complex. Although Notch signalling can play both oncogenic and tumour-suppressor roles in solid tumours, in the haematopoietic system it is exclusively oncogenic, notably in T-cell acute lymphoblastic leukaemia, a disease characterized by Notch1-activating mutations. Here we identify novel somatic-inactivating Notch pathway mutations in a fraction of patients with chronic myelomonocytic leukaemia (CMML). Inactivation of Notch signalling in mouse haematopoietic stem cells (HSCs) results in an aberrant accumulation of granulocyte/monocyte progenitors (GMPs), extramedullary haematopoieisis and the induction of CMML-like disease. Transcriptome analysis revealed that Notch signalling regulates an extensive myelomonocytic-specific gene signature, through the direct suppression of gene transcription by the Notch target Hes1. Our studies identify a novel role for Notch signalling during early haematopoietic stem cell differentiation and suggest that the Notch pathway can play both tumour-promoting and -suppressive roles within the same tissue.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/,
http://linkedlifedata.com/resource/pubmed/grant/1P01CA97403,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA105129-07,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA133379-04,
http://linkedlifedata.com/resource/pubmed/grant/R01 CA149655-03,
http://linkedlifedata.com/resource/pubmed/grant/R01CA105129,
http://linkedlifedata.com/resource/pubmed/grant/R01CA1328234,
http://linkedlifedata.com/resource/pubmed/grant/R01CA133379,
http://linkedlifedata.com/resource/pubmed/grant/R01CA149655,
http://linkedlifedata.com/resource/pubmed/grant/R21 CA141399-02,
http://linkedlifedata.com/resource/pubmed/grant/R21CA141399,
http://linkedlifedata.com/resource/pubmed/grant/U54CA143798
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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 |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1476-4687
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pubmed:author |
pubmed-author:Abdel-WahabOmarO,
pubmed-author:AifantisIannisI,
pubmed-author:AraldiElisaE,
pubmed-author:BeranMiroslavM,
pubmed-author:BuonamiciSilviaS,
pubmed-author:CathelinSeverineS,
pubmed-author:EfstratiadisArgirisA,
pubmed-author:HaenoHiroshiH,
pubmed-author:IbrahimSherifS,
pubmed-author:KlinakisApostolosA,
pubmed-author:LevineRoss LRL,
pubmed-author:LiuCynthiaC,
pubmed-author:LobryCamilleC,
pubmed-author:MichorFranziskaF,
pubmed-author:OhPhilmoP,
pubmed-author:TaghonTomT,
pubmed-author:TrimarchiThomasT,
pubmed-author:ZavadilJiriJ,
pubmed-author:van De WalleIngeI
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pubmed:issnType |
Electronic
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pubmed:day |
12
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pubmed:volume |
473
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
230-3
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pubmed:dateRevised |
2011-11-14
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pubmed:meshHeading |
pubmed-meshheading:21562564-Animals,
pubmed-meshheading:21562564-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:21562564-Cell Differentiation,
pubmed-meshheading:21562564-Cells, Cultured,
pubmed-meshheading:21562564-Gene Expression Profiling,
pubmed-meshheading:21562564-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21562564-Gene Silencing,
pubmed-meshheading:21562564-Genes, Tumor Suppressor,
pubmed-meshheading:21562564-Granulocyte-Macrophage Progenitor Cells,
pubmed-meshheading:21562564-Hematopoietic Stem Cells,
pubmed-meshheading:21562564-Homeodomain Proteins,
pubmed-meshheading:21562564-Humans,
pubmed-meshheading:21562564-Leukemia, Myelomonocytic, Chronic,
pubmed-meshheading:21562564-Mice,
pubmed-meshheading:21562564-Mice, Inbred C57BL,
pubmed-meshheading:21562564-Mutation,
pubmed-meshheading:21562564-Receptors, Notch,
pubmed-meshheading:21562564-Signal Transduction,
pubmed-meshheading:21562564-Tumor Cells, Cultured
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pubmed:year |
2011
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pubmed:articleTitle |
A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia.
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pubmed:affiliation |
Biomedical Research Foundation, Academy of Athens, Athens, Greece.
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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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