Figure 4.
The ASXL1G643W variant affects the expression of leukemia relevant pathways. (A). Volcano plot depicting gene expression changes in Asxl1G643W/G643W; CebpaΔ/p30 vs. Asxl1+/+; CebpaΔ/p30 leukemic blasts. (B-C). GSEA plots for selected gene sets which are either upregulated (B) or downregulated (C) in Asxl1G643W/G643W; CebpaΔ/p30 versus Asxl1+/+; CebpaΔ/p30 leukemic blasts. (D) Boxplots showing the CHIP-signal levels of selected marks surrounding the TSS (+/- 500 bp) for genes that are either up- or downregulated in Asxl1G643W/G643W; CebpaΔ/p30 vs. Asxl1+/+; CebpaΔ/p30 leukemic blasts (Online Supplementary Table S1). The data is derived from a previous CEBPA mutant (Cebpap30/p30, Asxl1 WT) dataset.22 Gene expression levels as determined by RNA sequencing are also indicated. Up: upregulated genes in Asxl1G643W/G643W vs. Asxl1+/+ leukemic blasts (false discovery rate [FDR] 0.05, log2FC>0, baseMean>10, n=105), down: downregulated genes in Asxl1G643W/G643W vs. Asxl1+/+; (FDR 0.05, log2FC <0, baseMean >10, n=201), neutral: neutral genes (-0.01 < log2FC<0.01, baseMean>10, n=165) in Asxl1G643W/G643W vs. Asxl1+/+. P-values levels *P<0.05s, **P=0.01, ***P=0.001 are indicated