Fig. 4
Combined targeting of BCL-2 and MCL1 improves the survival of mice xenografted with human AML (a) 24 irradiated NSG mice were transplanted with 105 human MV4;11 cells transduced with a luciferase reporter construct. AML engraftment was confirmed by bioluminescence imaging on day 7. On day 10 (arrow), mice were divided into treatment groups of six mice and treated with (i) vehicle, (ii) S55746 100 mg/kg by oral gavage daily (5 days/week for 4 weeks), (iii) S63845 25 mg/kg IV twice weekly for 4 weeks, or (iv) combination S55746/S63845 for 4 weeks, with treatment ending on day 35. b Similar experiment as in (A) using OCI-AML3 cells transduced with a luciferase reporter. Engraftment was confirmed on day 32. Treatment commenced on day 38 (arrow) post-transplant for a total of 7 weeks. c NSG mice engrafted with human MV4;11 and treated as in (a) and followed for Kaplan–Meier (KM) survival (ethical endpoints) showing that combined treatment with S55746/S63845 resulted in significantly longer survival than vehicle control (arrows show start and end of treatment). d KM survival of NSG mice engrafted with human OCI-AML3 cells and treated as in (a) showing that combined treatment with S55746/S63845 resulted in significantly longer survival than vehicle control (arrows show start and end of treatment)
