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

Research output: Contribution to journalArticlepeer-review


  • 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
  • Claus Nerlov
  • Jörg Cammenga
  • Borja Saez
  • David T Scadden
  • Min Ye
  • Daniel G Tenen

Colleges, School and Institutes

External organisations

  • Harvard Medical School


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.

Bibliographic note

Copyright © 2013 Elsevier Inc. All rights reserved.


Original languageEnglish
Pages (from-to)575-588
Number of pages14
JournalCancer Cell
Issue number5
Publication statusPublished - 11 Nov 2013


  • 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