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

作者：Zhang Hong; Alberich Jorda Meritxell; Amabile Giovanni; Yang Henry; Staber Philipp B; DiRuscio Annalisa; Welner Robert S; Ebralidze Alexander; Zhang Junyan; Levantini Elena; Lefebvre Veronique; Valk Peter J M; Delwel Ruud; Hoogenkamp Maarten; Nerlov Claus; Cammenga Jorg; Saez Borja; Scadden David T; Bonifer Constanze; Ye Min^*; Tenen Daniel G

来源：Cancer Cell, 2013, 24(5): 575-588.

DOI：10.1016/j.ccr.2013.09.018

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.

• 出版日期2013-11-11