Figure 6.
IL-7R signaling is essential for Notch1-induced T-ALL pathogenesis. BM Lin− c-kit+ HPCs isolated from wt or Il7r−/− H2-Kb+ mice were transduced with lentiviral vectors encoding ICN1 and GFP and transplanted into H2-Kb− immunodeficient mice. (A) CD4 and CD8 expression of electronically gated transduced (ICN1+) and nontransduced (ICN1−) H2-Kb+Il7r wt or Il7r−/− donor cells engrafting the BM of transplanted mice at 4 weeks posttransplant. Results are representative of 1 of ≥18 mice per group (n = 3). Engraftment potential of ICN1-transduced (B) and total H2-Kb+ (C) donor cells. Data are percentages (mean ± standard error of the mean [SEM]) of donor cells recovered from the peripheral blood of ≥18 mice per group at 4 weeks posttransplant (n = 3). (D) Percentages of myeloid-lineage (CD11b+ or Gr1.1+), B-lineage (B220+), T-lineage (DP; CD4+CD8+ and/or CD8+CD4−) or Lin− (CD11b−, Gr1.1−, B220−, CD4−, CD8−) cells derived from transduced (ICN1+) and nontransduced (ICN1−) donor cells engrafting the spleen of transplanted mice at 5 weeks posttransplant. Mean ± SEM values from ≥18 mice per group are shown (n = 3). (E) Kaplan-Meier survival curves of immunodeficient mice transplanted with wt or Il7r−/− BM HPCs transduced with ICN1. (F) Percentages of ICN1+ transduced cells recovered at 5 weeks posttransplant from the indicated organs of immunodeficient mice transplanted with wt or Il7r−/− BM HPCs. Mean ± SEM percentages of ≥14 mice per group are shown (n = 3). **P < .01, ***P < .001. ns, not significant.