Fig. 6

Coordination of HSP90, MYC, and CDK9 drives therapeutic resistance. A Violin plots show inferred cellular pathway activity of MYC_TARGETS_v1 and MYC_TARGETS_v2 across the BTKi-R and Dual-R groups. HSP90AB1 is a part of the MYC_TARGETS_v1 gene set. To avoid bias, we removed it from the MYC_TARGETS_v1 gene set. B Boxplots show intra-sample correlation coefficients between HSP90AB1 expression and MYC_TARGETS_v1 activity in the BTKi-R and Dual-R groups. Each dot represents the correlation between HSP90AB1 expression and MYC_TARGETS_v1 activity across the individual cells within a single sample. C Barplots show increased correlation between HSP90AB1 and MYC activities in longitudinal samples. D Plots show the correlation between HSP90AB1 and MYC dependencies (y-axis) for all genes in DepMap (y-axis) across all cancer cell lines (top) and restricted to lymphoma cell lines (bottom). Red vertical line marks the position of HSP90AB1 in genome-wide ranking of genes based on correlation with MYC. E Violin plots show increased HSP90AB1 dependency (y-axis) across lymphoma cell lines divided into MYC-dependent and -independent groups (x-axis). Low values indicate greater dependency. F Barplot shows HSP90AB1 dependency (y-axis) across select lymphoma cell lines (x-axis). Colors indicate MYC dependency. G Scatter plot shows the correlation of MYC and HSP90AB1 RNA-seq expression across tumors in the TCGA DLBCL cohort. H Scatter plot shows the correlation of CDK9 expression and MYC activities at pseudobulk level