Activation of MYC signaling in SF3B1 mutant chronic lymphocytic leukemia (CLL). A, Transcriptional regulation network of significantly enriched master regulators. Nodes indicate transcription factors or target genes differentially expressed between SF3B1 mutant and WT CLL. B, Venn diagram showing the overlap of MYC targets and differentially expressed genes in SF3B1 mutant samples (hypergeometric test; P = 8.1e-08 for positive regulated genes; P = 9.5e-29 for negative regulated genes). C, Results of pre-ranked GSEA enrichment analysis on MYC target genes. Genes up/down-regulated in SF3B1 mutant CLL were tested against a pre-ranked gene list which was generated based on the correlation with MYC. D, Heatmap of unsupervised clustering of differentially expressed genes based on SF3B1 genotype. Analyses in B, C, and D were performed using an expression matrix of 294 CLL patients from ICGC Data Portal (Z-score > 0 represents upregulation in SF3B1 mutant samples). ***P < 0.001.