Genetic loss of Sh2b3 accelerates NOTCH1-induced T-ALL. (A) Representative plots (of one of 6 animals per group) and quantification of GFP-expressing preleukemic cells in peripheral blood of mice transplanted with either Sh2b3^−/− or wild-type hematopoietic progenitors infected with retroviruses expressing ΔE-NOTCH1. (B) Representative plots (of one of 6 animals per group) and quantification of double-positive (CD4⁺CD8⁺; DP) cells in mice 3 weeks after transplantation. (C) Kaplan-Meier survival curves of mice transplanted with Sh2b3^−/− (n = 6) or wild-type (n = 6) hematopoietic progenitors expressing ΔE-NOTCH1. (D) Western blot analysis of Stat3 phosphorylation in NOTCH1-induced tumors generated from hematopoietic precursors from Sh2b3 wild-type and Sh2b3^−/− mice. (E) Heat map diagram of top ranking differentially expressed genes by the Student t test in Sh2b3^−/− (n = 3) vs Sh2b3 wild-type (n = 3) NOTCH1-induced leukemias. Genes in the heat map are shown in rows, and each individual sample is shown in 1 column. The scale bar shows color-coded differential expression, with red indicating higher levels of expression and blue indicating lower levels of expression. (F) GSEA enrichment plots of gene sets related to autoimmunity, immune function, and stem cells associated with the Sh2b3^−/− NOTCH1–induced leukemia signature.