Figure 4.
Figure 4. MEPs deficient for p53 and expressing oncogenic Nras are transformed to AML-initiating cells. Control and NrasG12D/+p53−/− mice were treated with pI-pC and euthanized on day 12 as described in “Materials and methods.” GMPs and MEPs were isolated from NrasG12D/+p53−/− bone marrow and transplanted to lethally irradiated mice as described in Table 1. Control recipients were transplanted with 2.5 × 105 total bone marrow cells (CD45.2+) from control mice and the same number of congenic bone marrow cells (CD45.1+). (A) Kaplan-Meier comparative survival analysis of recipient mice. Cumulative survival was plotted against days after transplantation. P value was determined by the log-rank test. (B) Quantification of spleen and liver weights in moribund AML mice transplanted with NrasG12D/+p53−/− MEPs and age-matched control recipients. (C) Complete blood count analysis of peripheral blood samples collected from moribund AML mice transplanted with NrasG12D/+p53−/− MEPs and age-matched control recipients. (D-F) Analysis of donor-derived (CD45.1–) (D) blast cells (c-Kit+), (E) myeloid progenitors, and (F) erythroid differentiation in BM and SP of moribund AML mice transplanted with NrasG12D/+p53−/− MEPs and age-matched control recipients. Data are presented as mean ± SD. **P < .01; ***P < .001. Hb, hemoglobin; HCT, hematocrit; PLT, platelet; RBC, red blood cell; WBC, white blood cell.

MEPs deficient for p53 and expressing oncogenic Nras are transformed to AML-initiating cells. Control and NrasG12D/+p53−/− mice were treated with pI-pC and euthanized on day 12 as described in “Materials and methods.” GMPs and MEPs were isolated from NrasG12D/+p53−/− bone marrow and transplanted to lethally irradiated mice as described in Table 1. Control recipients were transplanted with 2.5 × 105 total bone marrow cells (CD45.2+) from control mice and the same number of congenic bone marrow cells (CD45.1+). (A) Kaplan-Meier comparative survival analysis of recipient mice. Cumulative survival was plotted against days after transplantation. P value was determined by the log-rank test. (B) Quantification of spleen and liver weights in moribund AML mice transplanted with NrasG12D/+p53−/− MEPs and age-matched control recipients. (C) Complete blood count analysis of peripheral blood samples collected from moribund AML mice transplanted with NrasG12D/+p53−/− MEPs and age-matched control recipients. (D-F) Analysis of donor-derived (CD45.1) (D) blast cells (c-Kit+), (E) myeloid progenitors, and (F) erythroid differentiation in BM and SP of moribund AML mice transplanted with NrasG12D/+p53−/− MEPs and age-matched control recipients. Data are presented as mean ± SD. **P < .01; ***P < .001. Hb, hemoglobin; HCT, hematocrit; PLT, platelet; RBC, red blood cell; WBC, white blood cell.

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