Fig. 1
Interrogating pro-survival dependency in AML using BH3-mimetic drugs alone and in combination. The sensitivity (LC50) of freshly derived primary samples to BH3-mimetics alone, or in equimolar combination, relative to chemotherapy (cytarabine and idarubicin) after 48 h exposure. Samples are separated according to whether patients were a chemotherapy naive or had b relapsed and refractory AML. The control cell viability of each AML sample after 48 h in DMSO is shown. The upper concentration of cytarabine tested was 100 µM and for other drugs 10 µM. A color bar grading the LC50 values for each drug in the heat map is shown. c MV4;11 and OCI-AML3 cells were treated with indicated drugs and the LC50 at 16 h determined. Where indicated, cells were pre-incubated with the caspase inhibitor QVD (50 μM) for 1 h prior to addition of the other drugs. d Synergistic interactions between S63845 combined with standard anti-leukemic drugs were assessed using an Excess Inhibition matrix according to the Loewe additivity model. Synergy scores (SS) are represented as the mean of n = 2; each experiment being performed in duplicate (SS = 0 represents an additive effect, SS > 2 represents synergy; hashed line and SS > 5 represents strong synergy; dotted line)
