E-GEOD-45430 - Sox4 is a key oncogenic target in C/EBPα mutant Acute Myeloid Leukemia
Released on 23 March 2013, last updated on 3 June 2014
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 down-stream 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 mutant C/EBPα 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 leukemias with a distinct LIC phenotype. K/L (bi-allelic Cebpa mutations) leukemic mice and Sox4 overexprssing leukemic mice were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the C57/BL6 wild type mice.
transcription profiling by array
Borja Saez, Constanze Bonifer, Daniel G Tenen, David T Scadden, Giovanni Amabile, Henry Yang, Hong Zhang, Junyan Zhang, Maarten Hoogenkamp, Meritxell Alberich-Jordà, Min Ye, Peter J Valk, Philipp B Staber, Rob Welner, Ruud Delwel, Véronique Lefebvre