Fig. 4

Sequential resistance to BTKi and CAR-T therapies is reflected by specific gene expression fingerprints. A Heatmap shows the expression profile of outcome-specific genes (rows) across samples. Columns represent averaged expression profile of random 10 cells for each sample. Bars on the top denote clinical outcomes (five groups). Bars on the left highlight the outcome specific genes (four groups). B Boxplots show the expression of three outcome-specific gene expression across samples for representative genes MYLIP, FAM177B, and DDX11. Each dot represents averaged expression profile of random 10 cells for each sample. C Heatmap shows the expression profile of genes (rows) with significant changes between the Dual-R and BTKi-R samples across both cohorts. Columns represent averaged expression profile of random 10 cells for each sample. Representative genes (CDK9 and POLR2C) are highlighted in red. D Boxplots show differential expression of CDK9 and POLR2C in Dual-R and BTKi-R samples of both cohorts. Each dot represents averaged expression profile of random 10 cells for each sample. E Bar plots summarize the enriched pathways in different contrasts. Top: BTKi-R vs BTKi-sensitive (BTKi-Fast/Slow). Bottom: Dual-R vs BTKi-R. F Boxplots show average pathway scores (y-axis) of MYC_TARGETS_v1, MYC_TARGETS_v2, and OXPHOS gene sets across clinical outcomes (x-axis). There is a progressive enrichment of MYC targets and the OXPHOS pathway across the clinical outcomes