Downregulation of known TP53 target genes in NFIA-ETO2–expressing TP53R248Q/+ EBs. (A) PCA of gene expression signatures of WT or TP53R248Q/+ EBs expressing NFIA-ETO2 (WT, red; and TP53R248Q/+, blue) grown in MM (dot) or 24 hours in DM (triangle). Each point represents one sample, colored and shaped based on its TP53 status (WT or TP53R248Q/+) and the medium in which the cells were cultured (MM vs DM), respectively. (B) Volcano plot showing DEGs in NFIA-ETO2–expressing WT- vs TP53R248Q/+ EBs grown in MM. Dysregulated genes are colored in red (FDR <0.05). (C) Volcano plot showing DEGs in NFIA-ETO2–expressing WT- vs TP53R248Q/+ EBs grown in DM for 24h. Dysregulated genes are colored in red (FDR <0.05). (D) Selected positive and negative GSEA enrichment scores of DEGs obtained in NFIA-ETO2–expressing TP53R248Q/+ EBs when compared with NFIA-ETO2–expressing WT EBs cultured in DM (p-adj <0.1). (E) Profile plots representing ATAC-seq signals from WT and TP53R248Q/+ NFIA-ETO2–expressing EBs. Profile-plots were focused on peaks centers with ±5 kb. The heatmap represents the hierarchical clustering of ATAC-seq signals, performed with WT and TP53R248Q/+ NFIA-ETO2–expressing EBs. Heatmaps were also focused on peak centers with ±5 kb. (F) BART-predicted transcription factors that most likely suppress the downregulated genes in TP53R248Q/+ NFIA-ETO2–expressing EBs. (G) Selected positive and negative GSEA enrichment scores of DEGs of patients with AEL with TP53 mutations vs patients with AEL without TP53 mutations (padj <0.05). Data from Iacobucci et al.8 (H) Mean expression (count per million) of DEG-up and DEG-down in patients with AEL with (red dots) or without (green dots) TP53 mutations. DEG-up and DEG-down are the gene signatures comprising significantly upregulated (left) and downregulated (right) found to be differentially expressed in NFIA-ETO2–expressing TP53R248Q/+ EBs. Shown are AEL RNA-seq samples from Iacobucci et al.8 (I) Relative mean expression of DEG-up and DEG-down in patients with AML with (red dots) or without (green dots) TP53 mutations. DEG-up and DEG-down are the gene signatures comprising significantly upregulated (left) and downregulated (right) found to be differentially expressed in NFIA-ETO2–expressing TP53R248Q/+ EBs. Shown are AML microarray samples from the TCGA project. BART, binding analysis for regulation of transcription,
