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

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Somerville TD,Wiseman DH,Spencer GJ,Huang X,Lynch JT,Leong HS,Williams EL,Cheesman E,Somervaille TC

doi

10.1016/j.ccell.2015.07.017

subject

Has Abstract

pub_date

2015-09-14 00:00:00

pages

329-42

issue

3

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(15)00269-X

journal_volume

28

pub_type

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