Figure 6.
Single compounds and ruxolitinib combinations across malignant NK-cell lines and healthy PBMCs. ZIP scores are given, representing the drug synergies across malignant NK-cell lines and PBMCs in viability (A) and toxicity (B) readout. PBMCs from 2 individuals (gray) are compared with either TP53-mutant (orange) or STAT3-mutant (teal) NK-cell lines. Each dot represents one NK-cell line or in PBMCs. Line is set to median, and bar represents standard deviation. %-viability and %-toxicity of 300 nM tipifarnib (C-D) or 300 nM idasanutlin (E-F) combined with 100 nM ruxolitinib are shown. Single measurement per cell line. Mean and standard deviation represent, in ruxolitinib single treatment, 6 technical replicates and in “PBMC,” mean of PBMCs from 2 individuals. Dose responses and 8 × 8 dose-range synergy matrices are provided in supplemental Data 2. Drug combinations and single-drug dose–response curves of PBMC populations in the presence of 10 ng/mL IL-2: NK cells (G,J), total leukocytes (H,K), and T cells (I,L). Each dot represents mean and error bars represent the range from single wells of 2 experiments of PBMCs from different individuals.

Single compounds and ruxolitinib combinations across malignant NK-cell lines and healthy PBMCs. ZIP scores are given, representing the drug synergies across malignant NK-cell lines and PBMCs in viability (A) and toxicity (B) readout. PBMCs from 2 individuals (gray) are compared with either TP53-mutant (orange) or STAT3-mutant (teal) NK-cell lines. Each dot represents one NK-cell line or in PBMCs. Line is set to median, and bar represents standard deviation. %-viability and %-toxicity of 300 nM tipifarnib (C-D) or 300 nM idasanutlin (E-F) combined with 100 nM ruxolitinib are shown. Single measurement per cell line. Mean and standard deviation represent, in ruxolitinib single treatment, 6 technical replicates and in “PBMC,” mean of PBMCs from 2 individuals. Dose responses and 8 × 8 dose-range synergy matrices are provided in supplemental Data 2. Drug combinations and single-drug dose–response curves of PBMC populations in the presence of 10 ng/mL IL-2: NK cells (G,J), total leukocytes (H,K), and T cells (I,L). Each dot represents mean and error bars represent the range from single wells of 2 experiments of PBMCs from different individuals.

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