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.
Original language | English |
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Pages (from-to) | 575-588 |
Number of pages | 14 |
Journal | Cancer Cell |
Volume | 24 |
Issue number | 5 |
DOIs | |
Publication status | Published - 11 Nov 2013 |
Bibliographical note
Copyright © 2013 Elsevier Inc. All rights reserved.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
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)