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

Summary, in English

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.

• Author: Hong Zhang; Meritxell Alberich-Jorda; Giovanni Amabile; Henry Yang; Philipp B. Staber; Annalisa DiRuscio; Robert S. Welner; Alexander Ebralidze; Junyan Zhang; Elena Levantini; Veronique Lefebvre; Peter J. M. Valk; Ruud Delwel; Maarten Hoogenkamp; Claus Nerlov; Jörg Cammenga; Borja Saez; David T. Scadden; Constanze Bonifer; Min Ye; Daniel G. Tenen
• Department/s: Division of Molecular Medicine and Gene Therapy; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2013
• Language: English
• Pages: 575-588
• Publication/Series: Cancer Cell
• Volume: 24
• Issue: 5
• Links: http://dx.doi.org/10.1016/j.ccr.2013.09.018
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cancer and Oncology
• Status: Published
• ISBN/ISSN/Other: ISSN: 1878-3686