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Cancer Cell. 2015 Sep 14;28(3):329-42. doi: 10.1016/j.ccell.2015.07.017.

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

Author information

1
Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
2
Computational Biology Support Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
3
Department of Diagnostic Paediatric Pathology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
4
Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK. Electronic address: tim.somervaille@cruk.manchester.ac.uk.

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.

PMID:
26373280
DOI:
10.1016/j.ccell.2015.07.017
[Indexed for MEDLINE]
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