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    The transcription factor PlagL2 activates Mpl transcription and signaling in hematopoietic progenitor and leukemia cells

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    Authors
    Landrette, Sean F.
    Madera, Dmitri
    He, Feng
    Castilla, Lucio H.
    UMass Chan Affiliations
    Department of Microbiology and Physiologic Systems
    Program in Gene Function and Expression
    Document Type
    Journal Article
    Publication Date
    2011-04-01
    Keywords
    Leukemia, Myeloid, Acute
    DNA-Binding Proteins
    Transcription Factors
    RNA-Binding Proteins
    Receptors, Thrombopoietin
    Oncogene Proteins, Fusion
    Core Binding Factor beta Subunit
    Gene Expression Regulation
    Genetics and Genomics
    
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    Link to Full Text
    http://dx.doi.org/10.1038/leu.2010.301
    Abstract
    Cytokine signaling pathways are frequent targets of oncogenic mutations in acute myeloid leukemia (AML), promoting proliferation and survival. We have previously shown that the transcription factor PLAGL2 promotes proliferation and cooperates with the leukemia fusion protein Cbfbeta-SMMHC in AML development. Here, we show that PLAGL2 upregulates expression of the thrombopoietin receptor Mpl, using two consensus sites in its proximal promoter. We also show that Mpl overexpression efficiently cooperates with Cbfbeta-SMMHC in development of leukemia in mice. Finally, we demonstrate that PlagL2-expressing leukemic cells show hyper-activation of Jak2 and downstream STAT5, Akt and Erk1/2 pathways in response to Thpo ligand. These results show that PlagL2 expression activates expression of Mpl in hematopoietic progenitors, and that upregulation of wild-type Mpl provides an oncogenic signal in cooperation with CBFbeta-SMMHC in mice.
    Source
    Leukemia. 2011 Apr;25(4):655-62. Epub 2011 Jan 25. Link to article on publisher's site
    DOI
    10.1038/leu.2010.301
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/43939
    PubMed ID
    21263445
    Notes

    Co-author Dmitri Madera is a student in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

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    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1038/leu.2010.301
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