C/EBPα overexpression in Kasumi-1 cells upregulates pathways repressed in primary t(8;21) samples. (A-B) GSEA based on RNA-seq of Kasumi1 after overexpression of C/EBPα. Enrichment of genes that are upregulated in this process in comparison with genes that are repressed in primary t(8;21) as compared with normal karyotype AML samples in both the (A) Verhaak et al cohort⁵²  and (B) The Cancer Genome Atlas (TCGA) cohort⁵³  of patients with AML. (C-D) Model of the C/EBPα-mediated override of t(8;21) and t(3;21) AML transcriptional networks. (C) t(3;21) and t(8;21) AML are epigenetically different AMLs, but (D) overexpression of C/EBPα results in upregulation (blue lines) of myeloid differentiation genes, which also become bound by the fusion proteins, and repression (red lines) of select genes required for stem cell function.