p53 deletion and Nras^G12D/+ induce a highly penetrant AML. (A-F) Lethally irradiated mice were transplanted with 2.5 × 10⁵ total bone marrow cells from control, p53^−/−, Nras^G12D/+, or Nras^G12D/+p53^−/− mice along with same number of competitor cells. (A) Kaplan-Meier comparative survival analysis of reconstituted mice. Cumulative survival was plotted against days after transplantation. P value was determined by the log-rank test. (B) Disease incidence in recipient mice transplanted with p53^−/−, Nras^G12D/+, or Nras^G12D/+p53^−/− cells. (C) Representative flow cytometry analysis of bone marrow (BM), spleen (SP), and peripheral blood (PB) cells from moribund AML Nras^G12D/+p53^−/− and age-matched control mice. Note: red blood cells were lysed by using ammonium chloride treatment before flow analysis. (D) Complete blood count was performed on peripheral blood samples collected from moribund AML Nras^G12D/+p53^−/− and age-matched control mice. The results are presented as range (median). (E) Spleen and liver weight of moribund AML Nras^G12D/+p53^−/− and control mice. (F) Representative spleen histologic hematoxylin and eosin–stained sections from moribund AML Nras^G12D/+p53^−/− and control mice. Arrowheads indicate immature blast cells. (G) 1 × 10⁶ bone marrow or 5 × 10⁶ spleen cells from moribund AML Nras^G12D/+p53^−/− mice were transplanted into sublethally irradiated mice. Kaplan-Meier comparative survival curve was plotted against days after transplantation. The results are presented as mean ± standard deviation (SD). ***P < .001. BMT, bone marrow transplantation.