Sox4 Is a Key Oncogenic Target in C/EBP
Menée in vitro et in vivo, cette éude met en évidence des mécanimes par lesquels, en conséquence d'une inactivation du facteur de transcription C/EBP
Mutation or epigenetic silencing of the transcription factor C/EBP
α 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/EBP
α 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.
"C/EBP
α represses Sox4 transcription in a DNA-binding-dependent manner
"
SOX4 is overexpressed in human AML samples with mutated or silent CEBPA
"
Sox4 mediates leukemic outgrowth due to defective C/EBPα in murine and human models
"
LICs in Sox4- or mutated C/EBPα-driven AML models share a gene expression signature
Cancer Cell 2013