(A) Proportion of events within splicing categories of the 192 differential splice events based on analysis of RNA-seq data from 7 normal B cell samples and 22 CLL samples (13 CLL-SF3B1^wt and 9 SF3B1^mut). (B) Distribution of splice events in 22 CLL samples compared with 7 CD19⁺ cells based on Δ percent spliced in (ΔPSI) values versus negative logarithmic P values (–log₁₀P) of all splicing changes. Pink and black dashed lines indicate thresholds of |ΔPSI| of 10% and FDR of 10% (i.e., –log₁₀P = 1) for significant splice changes. Blue frequency bars indicate the number of significantly differential events in CLL as compared with normal B cells, of a total of 192. Light blue bars indicate nonsignificant events falling within the –10 < PSI < 10 interval. (C) PSI values of the 87 intron retention events within the 192 most differential splicing displayed in panel A. P value was calculated by Mann Whitney U test. (D) Total number of the top tenth percentile outlier splicing events across normal B cell and CLL samples, based on RNA-seq analysis. Reported P values were calculated by Welch t test with Bonferroni correction. (E) Pathway enrichment analysis by the Panther algorithm of the 192 most differential splicing events between CLL and normal B cells (black) and the CLL-specific splicing outliers represented in at least 7 of the 22 CLL samples (blue). Significantly enriched pathways within each category and respective –log₁₀P values are indicated in the figure. (F) Percentage viability of CD19⁺ cells from 5 healthy donor PBMCs, 10 SF3B1^wt CLL samples, and 10 SF3B1^mut CLL samples after 8 hours of treatment with increasing concentrations of E7107 (1 nM to 1 μM). Reported P values were calculated by 1-way ANOVA with Scheffé’s correction.