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. 2018 May 22;9(39):25647–25660. doi: 10.18632/oncotarget.25429

Figure 6. MC2884 induces apoptosis in hrAPLs and alters the epigenome.

Figure 6

(A) Analysis of cell death (% of cells in pre-G1 phase) induced by MC2884, HDACi (MS275 and/or SAHA) and ATRA in ex vivo APL blasts (24 h). (B) Heatmap showing H3K27ac changes at promoter and enhancer regions upon ex vivo MC2884 treatment of hrAPL (pt#8) cells. (C) Overview of epigenetic changes at the BCL2, AK2 and SEC23A genomic regions in control or MC2884 ex vivo treated hrAPL cells. (D) (Left) Boxplot and (Right) heatmap showing H3K27ac changes at enhancer regions that show reduced occupancy levels after ex vivo MC2884 treatment of a hrAPL sample. * indicates significance at p < 0.01. (E) Table showing functional annotation of genes associated with enhancers that have reduced H3K27ac after ex vivo MC2884 treatment of hrAPL (pt#8). (F) Heatmap showing H3K27me3 changes at genomic regions upon ex vivo MC2884 treatment of hrAPL cells. (G) Overview of H3K27ac at the EZH2 gene in control or MC2884 ex vivo treated hrAPL cells; (H) Expression of genes associated with enhancers (distance to gene <50 kb and RPKM sum >100; left) reduced in H3K27ac or of genes associated with promoters with reduced H3K27me3 (RPKM sum > 0.5; right). * indicates significance at p < 0.01.