title: 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.
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Tim D D
authors.initials: TD
authors.lastname: Somerville
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wiseman
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Spencer
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: James T
authors.initials: JT
authors.lastname: Lynch
authors.affiliation: Computational Biology Support Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Hui Sun
authors.initials: HS
authors.lastname: Leong
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Williams
authors.affiliation: Department of Diagnostic Paediatric Pathology, Royal Manchester Children's Hospital, Manchester M13 9WL, UK.
authors.forename: Edmund
authors.initials: E
authors.lastname: Cheesman
authors.affiliation: Leukaemia Biology Laboratory, Cancer Research UK Manchester Institute, The University of Manchester, Manchester M20 4BX, UK. Electronic address: tim.somervaille@cruk.manchester.ac.uk.
authors.forename: Tim C P
authors.initials: TC
authors.lastname: Somervaille
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; C097899:homeobox protein HOXA9