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    Frequent derepression of the mesenchymal transcription factor gene FOXC1 in acute myeloid leukemia.

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    Authors
    Somerville, Tim D D
    Wiseman, Daniel H
    Spencer, Gary J
    Huang, Xu
    Lynch, James T
    Leong, Hui Sun
    Williams, Emma L
    Cheesman, E
    Somervaille, Tim C P
    Affiliation
    Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK
    Issue Date
    2015-09-14
    
    Metadata
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    Abstract
    Through in silico and other analyses, we identified FOXC1 as expressed in at least 20% of human AML cases, but not in normal hematopoietic populations. FOXC1 expression in AML was almost exclusively associated with expression of the HOXA/B locus. Functional experiments demonstrated that FOXC1 contributes to a block in monocyte/macrophage differentiation and enhances clonogenic potential. In in vivo analyses, FOXC1 collaborates with HOXA9 to accelerate significantly the onset of symptomatic leukemia. A FOXC1-repressed gene set identified in murine leukemia exhibited quantitative repression in human AML in accordance with FOXC1 expression, and FOXC1(high) human AML cases exhibited reduced morphologic monocytic differentiation and inferior survival. Thus, FOXC1 is frequently derepressed to functional effect in human AML.
    Citation
    Frequent derepression of the mesenchymal transcription factor gene FOXC1 in acute myeloid leukemia. 2015, 28 (3):329-42 Cancer Cell
    Journal
    Cancer Cell
    URI
    http://hdl.handle.net/10541/581073
    DOI
    10.1016/j.ccell.2015.07.017
    PubMed ID
    26373280
    Type
    Article
    Language
    en
    ISSN
    1878-3686
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ccell.2015.07.017
    Scopus Count
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