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    Proteomic analysis reveals a novel mechanism induced by the leukemic oncogene Tel/PDGFRβ in stem cells: activation of the interferon response pathways.

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    Authors
    Dobbin, E
    Graham, C
    Freeburn, R
    Unwin, Richard D
    Griffiths, John R
    Pierce, Andrew
    Whetton, Anthony D
    Wheadon, H
    Affiliation
    Paul O'Gorman Leukaemia Research Centre, University of Glasgow, Glasgow, G12 0YN, UK.
    Issue Date
    2010-11
    
    Metadata
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    Abstract
    Objective proteomic analysis offers opportunities for hypothesis generation on molecular events associated with pathogenesis in stem cells. Relative quantification mass spectrometry was employed to identify pathways affected by Tel/PDGFRβ, an oncogene associated with myeloproliferative neoplasia (MPN). Its effects on over 1800 proteins were quantified with high confidence. Of those up-regulated by Tel/PDGFRβ several were involved in the interferon gamma (IFNγ) response. To validate these observations we employed embryonic and myeloid stem cells models which revealed Tel/PDGFRβ-induced STAT1 up-regulation and activation was responsible for modulating the interferon response. A STAT1 target highly up-regulated was ICSBP, a transcriptional regulator of myeloid and eosinophilic differentiation. ICSBP interacts with CBP/p300 and Ets transcription factors, to promote transcription of additional genes, including the Egr family, key regulators of myelopoiesis. These interferon responses were recapitulated using IFNγ stimulation of stem cells. Thus Tel/PDGFRβ induces aberrant IFN signaling and downstream targets, which may ultimately impact the hematopoietic transcriptional factor network to bias myelomonocytic differentiation in this MPN.
    Citation
    Proteomic analysis reveals a novel mechanism induced by the leukemic oncogene Tel/PDGFRβ in stem cells: activation of the interferon response pathways. 2010, 5 (3):226-43 Stem Cell Res
    Journal
    Stem Cell Research
    URI
    http://hdl.handle.net/10541/120147
    DOI
    10.1016/j.scr.2010.08.001
    PubMed ID
    20875954
    Type
    Article
    Language
    en
    ISSN
    1876-7753
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.scr.2010.08.001
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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