Fig. 2: GNE/BMS synergy in different cell systems.

A The indicated cell lines were treated with GNE and BMS (Supplementary Table 2) either alone or in combination and cell densities were quantified by crystal violet staining. Synergistic inhibition of cell proliferation was calculated by determination of the Coefficient of Drug Interaction (CDI). CDI values ≥ 0.7 (indicated by a blue-dotted line) were considered to lack synergistic activity, while cells showing CDI values ≤ 0.4 show high synergy. B Primary germinal center B cells were transduced with MYC-BCL2 or BCL6-BCL2 and treated with sublethal concentrations of GNE and BMS (Supplementary Table 2). After 7 days, cell number was determined and the average CDI score calculated, n = 4. C Left: KRAS^G12V/MYC cells were grown in soft agar for 5 days to allow colony formation, followed by administration of GNE and BMS, which was repeated one week later. After 12 days, cells were stained with crystal violet. Scale bar = 30 µm. Right: Quantification of soft agar colony formation experiments. Shown are mean ± SD, n = 3, two-way ANOVA with Dunnett’s multiple comparisons test. D Patient-derived colorectal cancer organoids were transduced with a lentivirus encoding Luciferase2-P2A-EGFP and selected with puromycin to enable stable expression. Organoids were harvested, singularized enzymatically and grown in 96-well round-bottom plates to organoids. Following treatment with GNE and/or BMS for 6 days (concentrations listed in Supplementary Table 2), with a repeated treatment after 3 days, organoids were analyzed by microscopy and cell viability was assessed using the ONE-GloEX assay. The average CDI scores of different tumor organoids are shown, n = 2. E The morphology of organoids from patient O20 responding to GNE/BMS treatment is shown as an example.