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

H Zhang, M Alberich-Jorda, G Amabile, H Yang, PB Staber, A DiRuscio, RS Welner, A Ebralidze, JY Zhang, E (Elena) Levantini, V Lefebvre, Peter Valk, Ruud Delwel, M Hoogenkamp, C Nerlov, J Cammenga, B Saez, DT Scadden, C Bonifer, M YeDG Tenen

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98 Citations (Scopus)

Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)575-588
Number of pages14
JournalCancer Cell
Volume24
Issue number5
DOIs
Publication statusPublished - 2013

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