Pan–Bcl-2 inhibition by (–)BI97D6 potently kills leukemia stem/progenitor cells at doses sparing normal hematopoietic stem/progenitor cells. (A-B) Representative FACS plots of (A) AML blast cells or (B) normal MNCs following treatment with 100 nM of (–)BI97D6 for 48 hours. (C-D) Change in live cell numbers (AnnV−/PI−) as a function of (–)BI97D6 concentration. Fresh AML or normal MNCs were isolated and treated with indicated doses of (–)BI97D6 for 48 hours. Live cell numbers were enumerated and normalized to untreated controls. (E) Diagram showing the experimental design. AML patient cells (1.0 × 106) were intravenously injected into NSG mice following 24-hour incubation with 100 nM (–)BI97D6 or DMSO (vehicle). (F) Representative FACS plots showing engraftment of human AML cells in mouse peripheral blood 6 weeks after injection. (–)BI97D6 pretreatment significantly reduced engraftment/progression of AML patient cells. (G) Kaplan-Meier survival curves for the mouse experiment described in E (5 mice per arm).
