Fig. 4. Vorinostat is synergistic with bortezomib in KMT2Ar leukemia.

A SEM cells were incubated for 8 h in 3 nM bortezomib, 1 µM vorinostat, or both followed by staining for acetylated tubulin (green) and vimentin (red) to visualize microtubules and aggresomes, respectively. Representative images are shown. 100 cells were scored per group by three individuals independently for the presence of aggresomes, average counts with the standard error of the mean are shown. Unpaired t test comparing bortezomib to bortezomib+vorinostat, two-tailed p value equals 0.0276. Source data are provided as a Source data file. B Cytotoxicity assay of bortezomib in combination with vorinostat. The KMT2Ar infant ALL cell line SEM and two patient samples were grown in the presence of bortezomib and vorinostat at the indicated concentrations for 72 h in technical triplicates. Viability was assessed by cell titer glo. Estimated effect of various levels of vorinostat in combination with bortezomib are shown. Curve shifts to the left indicate potentiation. EC50 values of bortezomib in the presence of varying concentrations of vorinostat are presented in Table 1. See Supplementary Fig. 17 for the best fit BRAID surface for each combination with estimated value of κ and confidence interval.