Extended Data Fig. 4: IKAROS degradation perturbs diverse cellular pathways.

a, RNA-seq dot-plot with linear regression showing z-score for differential gene expression correlating LEN (5 μM) and CC220 (1 μM) treatment for 3 days. b, RNA-seq volcano plot for MV4;11 treated with LEN for 6 days. c, GSEA results for ‘oncogenic signatures’ for RNA-seq data on Day 3. Dot plot is shown of the log10 false discovery rate (FDR) q-value and normalized enrichment score (NES) as determined by GSEA computational method. d, GSEA results for ‘Hallmarks’ signatures. Dot plot is shown of the log10 false discovery rate (FDR) q-value and normalized enrichment score (NES) as determined by the GSEA computational method. e, Bar code plots created using the GSEA tool for putative MLL-fusion target genes with selected genes from leading edge analysis indicated with adj-p-value<0.05 in MOLM13 or MV4;11. Normalized enrichment score and family-wise error rate p-value as determined by GSEA computational method. f, Gene expression z-score heatmap for selected genes within immune regulatory and inflammatory pathways under treatment with CC220 (n = 3) compared to DMSO-treated control (n = 3). g, Venn diagram for genes displaying > 2-fold change in expression following CC-220 treatment comparing cell lines. Gene number and percentage overlap is indicated. Selected genes deregulated in both cell lines are indicated. h, Correlation of IKAROS-bound gene TSSes, determined by ChIP-seq, with RNA-seq changes. Bar code plot showing gene expression changes following treatment with CC220 (3 days) for the top 500 genes bound by IKAROS (by peak enrichment over background). Selected genes from leading edge analysis indicated. Normalized enrichment score and family-wise error rate p-value determined by GSEA computational method. i, Correlation of IKAROS-bound enhancers, determined by ChIP-seq and the ABC prediction tool, with RNA-seq gene expression changes. Bar code plots display gene expression changes following treatment with CC-220 (3 days) for the top 500 genes predicted to be regulated by IKAROS-bound enhancers (by peak enrichment over background at enhancers). Normalized enrichment score and family-wise error rate p-value determined by GSEA computational method. Venn diagram for overlap between gene expression change and genes predicted to be regulated by the top 1000 IKAROS-bound enhancers.