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

Somerville, T. D.D., Wiseman, D. H., Spencer, G. J., Huang, X. , Lynch, J. T., Leong, H. S., Williams, E. L., Cheesman, E. and Somervaille, T. C.P. (2015) Frequent derepression of the mesenchymal transcription factor gene FOXC1 in acute myeloid leukemia. Cancer Cell, 28(3), pp. 329-342. (doi: 10.1016/j.ccell.2015.07.017) (PMID:26373280)

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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 FOXC1high human AML cases exhibited reduced morphologic monocytic differentiation and inferior survival. Thus, FOXC1 is frequently derepressed to functional effect in human AML.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Huang, Dr Xu
Authors: Somerville, T. D.D., Wiseman, D. H., Spencer, G. J., Huang, X., Lynch, J. T., Leong, H. S., Williams, E. L., Cheesman, E., and Somervaille, T. C.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier
ISSN:1535-6108
ISSN (Online):1878-3686
Published Online:14 September 2015

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