The acute myeloid leukemia associated AML1-ETO fusion protein alters the transcriptome and cellular progression in a single-oncogene expressing in vitro induced pluripotent stem cell based granulocyte differentiation model

Here we describe the development and characterization of an induced pluripotent stem cell (iPSC) system that allows in vitro differentiation towards different mature myeloid cell types such as monocytes and granulocytes. During in vitro differentiation we inducible expressed the AML1-ETO fusion protein and examined the effects of the oncoprotein on differentiation and the underlying alterations in the gene program. Our analysis revealed that AML1-ETO as a single oncogenic hit in a presumable non-mutated background blocks granulocytic differentiation and deregulates the gene program via altering the acetylome of the differentiating granulocytic cells and inducing t(8;21) AML associated leukemic characteristics. Transcriptome analysis and H3K27ac ChIP-seq of control and AML1-ETO induced iPSCs was performed using illumina high-throughput sequencing