Fig. 2.

Targeted increase of p53 protein level ameliorates FA leukemia burden. a Nutlin-3 treatment ameliorates splenomegaly. We transplanted 1–3 × 10⁶ BM cells from the AML-3 patient by intra-femoral injection into sublethally irradiated NSGS recipient mice. The mice were treated with Nutlin-3 at a dose of 50 mg/kg daily beginning at 6 weeks post-transplant for 2 weeks. Quantification of spleen weights and representative spleen images of the recipient mice are shown (n = 6 per group). b Nutlin-3 treatment inhibits myeloid expansion. BM cells from the recipient mice in a were subjected to flow cytometric analysis for human cell contents. Quantification of myeloid (CD33⁺) cells in total human engraftment (hCD45⁺) is shown (n = 6 mice per group). c Nutlin-3 treatment elevates p53 protein level. The levels p53 protein in human-derived BM cells (hCD45⁺) from three vehicle-treated and three Nutlin-3-treated recipient mice in a were analyzed by immunoblotting using antibodies for p53 or β-actin. The relative levels of p53 to β-actin are indicated below the blot. d Nutlin-3 treatment delays leukemia development. Cells (5 × 10⁶) isolated from the BM of the primary recipients in a were injected intrafemorally into each NSGS secondary recipient m ouse (n = 6–9 for each group). Survival of the recipients was monitored and plotted by Kaplan–Meier curve method. The error bars and asterisks in Fig. 2a, b represent means ± SD and ∗p < 0.05, respectively