Effects of JAK inhibition and synergy with BCL2 inhibition are mediated in part by induction of apoptosis by caspase-3/7 and caspase-8. (A) Representative curves of caspase 3/7 activity at 4 hours (i), 12 hours (ii), and 24 hours (iii) shown for patient 9 after incubation with ruxolitinib and venetoclax. (B) Caspase-8 activity at 4 hours (i), 12 hours (ii), and 24 hours (iii) shown for patient 9 after incubation with ruxolitinib and venetoclax. Significant increase in caspase-3/7 activity reflecting total apoptosis, and caspase-8 activity reflecting extrinsic apoptosis, was seen with combination therapy compared with either ruxolitinib or venetoclax alone at all concentrations and time points tested. *P < .05; **P < .01; ***P < .001  (P value against ruxolitinib). †P < .05; ††P < .01; †††P < .001 (P value against venetoclax).