Fig. 1: Human T-ALL pathogenesis induced by active NOTCH1 involves a developmental arrest at the β-selection checkpoint.

a, Schematic of the experimental design for de novo generation of human T-ALL. Sublethally irradiated NSG mice were subjected to i.v. injection with human cord blood (CB) CD34⁺ HPCs (1–1.5 × 10⁵ cells per mouse) retrovirally transduced with either ICN1 along with GFP, or GFP alone as the control. b, Representative flow cytometry expression of CD4, CD8, CD3, TCRαβ and TCRγδ by ICN1⁺ human T-ALL cells infiltrating the bone marrow of diseased mice in a at 27 weeks after transplant. c, Representative CD3 versus TCRαβ expression of human ICN1⁺ T-ALL cells recovered from diseased mice in a (primary), or from NSG mice after serial transplantation with bone marrow from primary mice (1st transfer and 2nd transfer). Results correspond to T-ALL cells isolated from the bone marrow at 39, 8 and 9 weeks after transplant, respectively. d, Mean percentages ± s.e.m. of human CD8⁺CD4⁺ double-positive, CD3^loTCRαβ^neg ICN1⁺ cells infiltrating the bone marrow of either primary diseased mice, or serially transplanted mice (nine mice per group from two independent experiments) as in c. Data were analyzed by one-way analysis of variance (ANOVA) with Kruskal–Wallis Dunn’s multiple-comparisons test. ****P < 0.0001.

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