Phosphoproteomic signature of duvelisib. (A) Workflow of the P100 targeted phosphoproteomic assay and data analysis. (B) Perturbation set enrichment analysis. Each column represents the indicated class of compounds. Each horizontal line in a column represents a single compound from that class. The ranked positions of connectivity compared with the duvelisib-sensitive or -resistant profile is shown for each compound in a class. q-values were computed using the unweighted preranked GSEA algorithm. BRDi, bromodomain inhibitors; ddPKi, DNA-dependent protein kinase inhibitors; genKi, general kinase inhibitor; p450i, cytochrome p450 inhibitor; PI3Ki, PI3 kinase inhibitor; SIRT1a, SIRT1 activator. (C) Immunoblot of the duvelisib-sensitive cell line OCI-LY13.2 and duvelisib-resistant cell lines SMZ1 after treatment with 1 µM duvelisib for 6 hours and 72 hours. (D) Quantification of cell cycle phases by Hoechst33342 staining and flow cytometry. (E) Dose response matrix and isobologram of 8 TCL cells lines treated with duvelisib in combination with the HDAC inhibitor romidepsin.