Sox4 Is a Key Oncogenic Target in C/EBPα Mutant Acute Myeloid Leukemia

Hong Zhang, Meritxell Alberich-Jorda, Giovanni Amabile, Henry Yang, Philipp B Staber, Annalisa Di Ruscio, Annalisa Diruscio, Robert S Welner, Alexander Ebralidze, Junyan Zhang, Elena Levantini, Véronique Lefebvre, Peter J M Valk, Ruud Delwel, Maarten Hoogenkamp, Claus Nerlov, Jörg Cammenga, Borja Saez, David T Scadden, Constanze BoniferMin Ye, Daniel G Tenen

Research output: Contribution to journalArticlepeer-review

83 Citations (Scopus)

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 languageEnglish
Pages (from-to)575-588
Number of pages14
JournalCancer Cell
Volume24
Issue number5
DOIs
Publication statusPublished - 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)

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