Fig. 5

AZD1775 sensitizes primary-derived ALL blasts to cytarabine and enhances apoptotic cell death. A Drug combination interactions between AZD1775 and AraC were investigated in high-risk and relapsed PDX samples (N = 8) in in vitro co-culture with hTERT-immortalized MSCs for 96 h. Excess over Bliss synergy was determined at each dose combination and quantified by most synergistic area scores (N = 1 for each respective sample in at least technical duplicate). B Representative dose–response matrix analyses showing cell inhibition (top) and synergistic landscape (bottom) across a range of AZD1775-AraC dose combinations individualized for each PDX sample. Grey dashed boxes indicate the most synergistic area. C Evaluation of apoptosis by Annexin-V staining with flow cytometry in PDX#4, PDX#10-r, PDX#15-r, and PDX#19-r following exposure to respective IC50s of AZD1775, AraC, or their combination for 48 h. Dots represent individual samples. Error bars indicate mean ± SD of compiled PDX data (N = 1 for each respective sample)