Sox4 is a key oncogenic target in C/EBPα mutant acute myeloid leukemia
| Autor: | David T. Scadden, Annalisa DiRuscio, Elena Levantini, Junyan Zhang, Daniel G. Tenen, Philipp B. Staber, Alexander K. Ebralidze, Claus Nerlov, Hong Zhang, Henry Yang, Meritxell Alberich-Jorda, Borja Saez, Giovanni Amabile, Min Ye, Véronique Lefebvre, Maarten Hoogenkamp, Peter J. M. Valk, Ruud Delwel, Jörg Cammenga, Robert S. Welner, Constanze Bonifer |
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| Přispěvatelé: | Cell biology, Hematology |
| Rok vydání: | 2013 |
| Předmět: |
Cancer Research
Myeloid Cellular differentiation Mutant Biology Article SOXC Transcription Factors SOX4 03 medical and health sciences Mice 0302 clinical medicine hemic and lymphatic diseases medicine Animals Humans Myeloid Cells Cells Cultured 030304 developmental biology Cell Proliferation Regulation of gene expression Mice Knockout 0303 health sciences Ccaat-enhancer-binding proteins Gene Expression Regulation Leukemic Myeloid leukemia Cell Differentiation Cell Biology Oncogenes medicine.disease Hematopoietic Stem Cells Molecular biology Leukemia Leukemia Myeloid Acute medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Gene Knockdown Techniques Mutation Cancer research CCAAT-Enhancer-Binding Proteins Neoplastic Stem Cells Transcriptome Neoplasm Transplantation |
| Zdroj: | Cancer Cell, 24(5), 575-588. Cell Press |
| ISSN: | 1878-3686 1535-6108 |
| Popis: | Mutation or epigenetic silencing of the transcription factor C/EBP alpha is observed in similar to 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 alpha whereby its expression is inversely correlated with C/EBP alpha 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/EBP alpha mutant AML models clustered together but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBP alpha inactivation contributes to the development of leukemia with a distinct LIC phenotype. |
| Databáze: | OpenAIRE |
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