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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.

Original publication

DOI

10.1016/j.ccr.2013.09.018

Type

Journal article

Journal

Cancer Cell

Publication Date

11/11/2013

Volume

24

Pages

575 - 588

Keywords

Animals, CCAAT-Enhancer-Binding Proteins, Cell Differentiation, Cell Proliferation, Cells, Cultured, Gene Expression Regulation, Leukemic, Gene Knockdown Techniques, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, Mice, Mice, Knockout, Mutation, Myeloid Cells, Neoplasm Transplantation, Neoplastic Stem Cells, Oncogenes, SOXC Transcription Factors, Transcriptome