title: Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia.
abstract: Mutation or epigenetic silencing of the transcription factor C/EBPα is observed in ∼10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but downstream targets relevant for leukemogenesis are not known. Here, we identify Sox4 as a direct target of C/EBPα whereby its expression is inversely correlated with C/EBPα activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia-initiating cells (LICs) from both Sox4 overexpression and murine C/EBPα mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBPα inactivation contributes to the development of leukemia with a distinct LIC phenotype.
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Meritxell
authors.initials: M
authors.lastname: Alberich-Jorda
authors.forename: Giovanni
authors.initials: G
authors.lastname: Amabile
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.forename: Philipp B
authors.initials: PB
authors.lastname: Staber
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Ruscio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Diruscio
authors.forename: Robert S
authors.initials: RS
authors.lastname: Welner
authors.forename: Alexander
authors.initials: A
authors.lastname: Ebralidze
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhang
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.forename: Véronique
authors.initials: V
authors.lastname: Lefebvre
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.forename: Ruud
authors.initials: R
authors.lastname: Delwel
authors.forename: Maarten
authors.initials: M
authors.lastname: Hoogenkamp
authors.forename: Claus
authors.initials: C
authors.lastname: Nerlov
authors.forename: Jörg
authors.initials: J
authors.lastname: Cammenga
authors.forename: Borja
authors.initials: B
authors.lastname: Saez
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Constanze
authors.initials: C
authors.lastname: Bonifer
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D022423:Myeloid Cells / Q000378:metabolism; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009857:Oncogenes; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors