GSE102730 C/EBP α overexpression overrides epigenetic reprogramming by RUNX1-ETO and RUNX1-EVI1 [RNA-seq]

Contributors : Justin Loke ; Paulynn S Chin ; Anna Pickin ; Peter Keane ; Salam A Assi ; Anetta Ptasinska ; Maria R Imperato ; Peter N Cockerill ; Constanze BoniferSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAcute myeloid leukemia (AML) is a heterogeneous disease caused by recurrent mutations in the transcription regulatory machinery. As a result, malignant myeloid cells display abnormal growth and are blocked in differentiation. One type of recurrent mutations affects RUNX1 which is subject to mutations and translocations, the latter giving rise to fusion proteins with aberrant transcriptional activities. We recently compared the mechanism by which the products of the t(8;21) and the t(3;21) translocation RUNX1-ETO and RUNX1-EVI1 globally reprogram the epigenome. We demonstrated that a main component of the block in differentiation in both types of AML is direct repression of the gene encoding for the crucial myeloid regulator C/EBP α by both fusion proteins. We also showed that CEBPA upregulation is required for the release of the differentiation block after oncogene knock-down. In the study presented here we examined at the global level the response of t(8;21) and t(3;21) cells to C/EBPα overexpression. We show that C/EBPα overexpression does not change oncoprotein expression or globally displace these proteins from their binding sites, but up-regulates a core set of common target genes important for myeloid differentiati...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research