ArrayExpress Uploader0mousewildtypewildtypewildtypeSox4 overexpressing leukemicSox4 overexpressing leukemicSox4 overexpressing leukemicK/L leukemicK/L leukemicK/L leukemic7216arrayexpress_sid6Mutation or epigenetic silencing of the transcription factor C/EBPα is observed in ~10% of patients with acute myeloid leukemia (AML). In...E-GEOD-45430/profile/8773/arrayexpressuploader19acute myeloid leukemialeukemiamyeloid leukemiaDec.12, 2014Falsesox4-is-a-key-oncogenic-target-in-cebp-mutant-acutE-GEOD-45430_A-AFFY-45Sox4 is a key oncogenic target in C/EBPα mutant Acute Myeloid LeukemiaNov.12, 2014Mutation 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.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-45430http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-45430/samples/