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Cancer Cell. 2013 Nov 11;24(5):575-88. doi: 10.1016/j.ccr.2013.09.018. Epub 2013 Oct 31.

Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia.

Author information

1
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

Erratum in

  • Cancer Cell. 2014 Feb 10;25(2):257. Diruscio, Annalisa [corrected to Di Ruscio, Annalisa].

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.

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PMID:
24183681
PMCID:
PMC4038627
DOI:
10.1016/j.ccr.2013.09.018
[Indexed for MEDLINE]
Free PMC Article

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