Depletion of Caspase-3 delays AE9a-driven leukemogenesis in the fetal liver transplantation model. (A) The strategy of the AE9a fetal liver transplantation model. (B) Lethally irradiated recipient mice were injected with WT or Caspase-3 knockout (Casp3^−/−) mouse E14.5 fetal liver cells transduced with AE9a. Loss of Caspase-3 prolongs the survival time of recipient mice. (178 days vs 122 days, n = 12, P < .001). (C-D) The AE9a-expressing cells proliferated less in the Caspase3^−/− group compared with the WT group. Shown is the percentage of GFP⁺ (AE9a-expressing) cells in peripheral blood at different time points after transplantation. (E) The average WBC count in AE9a-Caspase-3^−/− group was lower compared with the AE9a-WT group 2 months after transplantation. (F) The peripheral blood Giemsa staining shows less leukemia blast cells in the AE9a-Caspase-3^−/− group compared with the AE9a-WT group 4 months after transplantation (scale bar, 10 μm). (G) The spleen size in the AE9a-Caspase-3^−/− group was smaller compared with that of the AE9a-WT group 4 months after transplantation. (H-I) The frequencies of CD45.2-GFP⁺ cells and GFP⁺c-Kit⁺ cells in AE9a-Caspase-3^−/− group were lower than in AE9a-WT group 4 months after transplantation. FSC, forward scatter; MSCV, murine stem cell virus.