Fig. 4: GNA13-deficient GCB-DLBCL cells are hypersensitive to BCL2 inhibitors.

A Volcano plot of FDA-approved drugs and bioactive compounds with known targets on SU-DHL4-shGNA13^Scr and SU-DHL4-shGNA13^UTR cells. Drug effect size ratio between SU-DHL4-shGNA13^Scr and SU-DHL4-shGNA13^UTR vs. statistical significance (P value) were plotted. Red and blue points indicate drug identified as differentially inhibited between the two types of cells. B Dose–response curves for SU-DHL4-shGNA13^Scr or SU-DHL4-shGNA13^UTR treated with AKT inhibitor MK-2206. C IC₅₀ of BCL2 inhibitors ABT-199 and ABT-263 in DLBCL cell lines with either wild-type (blue dots) or mutant (red dots) GNA13. D Dose–response curves for SU-DHL4 and OCI-LY1 cells treated with ABT-199. E SU-DHL4 or OCI-LY1 cells were transfected with constructs containing shGNA13-600, shGNA13-UTR, or a scrambled shRNA (Scr). Levels of total (T)-AKT and phosphorylated (P)-AKT^S473 in these cells were examined by western blot analysis. GAPDH was used as loading controls. F Western blot analysis of BCL2, total (T)-AKT, and phosphorylated (P)-AKT^S473 level in SU-DHL4 cells treated with PI3K inhibitors Copanlisib or GDC-0941 at indicated concentrations for 6 h, respectively. G Western blot analysis of BCL2 level in SU-DHL4-shGNA13^Scr or SU-DHL4-shGNA13^UTR cells treated with PI3K inhibitors Copanlisib or GDC-0941 at indicated concentrations for 6 h, respectively. α-Tubulin was used as a loading control.