Frequent Derepression of the Mesenchymal Transcription Factor Gene FOXC1 in Acute Myeloid Leukemia.

Timothy Somerville, Daniel Wiseman, Gary Spencer, Xu Huang, James Lynch, Hui Sun Leong, Emma Williams, E Cheesman, Tim Somervaille

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)329-342
Number of pages13
JournalCancer Cell
Volume28
Issue number3
DOIs
Publication statusPublished - 14 Sept 2015

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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