β-Catenin leukemias are Notch independent. (A) Transcriptome profiling of control cells (n = 2), pretransformed (n = 3) DP cells, and total R26-βcat tumor cells (n = 4). Genes under- or overexpressed in tumors were selected with a fold change of expression >3 (P < .01, Student t test) compared with pretransformed or control cells. Expression changes are color-coded: red indicates upregulation and green downregulation. (B) Transcriptome comparison of R26-βcat tumors with tumors from 2 other T-ALL mouse models and DP thymocytes. Ik^L/L tumors are from mice hypomorphic for Ikaros²⁴ ; Tel-Jak2 tumors are from transgenic mice expressing the Tel-Jak2 fusion protein.²⁵  Genes up- or downregulated in R26-βcat tumors compared with other T-ALL tumors were selected with a fold change of expression >2. CD44 and Notch target genes are annotated. (C) The 149.4 cell line derived from an R26-βcat tumor and the T29 cell line derived from an Ik^L/L T cell tumor were transduced with Mig-R1 or Mig-dnMAML1 at day 0 and cultured for 7 days. Transduced cells expressed GFP. The percentage of GFP⁺ cells is shown over 7 days of culture. (D) Survival curve of mice transplanted with 10⁴ GFP⁺ or GFP⁻ cells from Mig-dnMAML1- or Mig-R1-transduced cultures. The experiment was stopped 60 days after the transplantation. (E) Western blot analysis for cleaved Notch1 (ICN1) expression in Ik^L/L, Ik^L/LR26-βcat, and Ik^L/+R26-βcat tumors and control Ik^L/+ thymocytes. (F) Flow cytometry analysis of intracellular Notch1 in T29 cells transduced with Mig-R1 or Mig-ΔGSK-βcatenin. GFP⁺ cells were sorted at day 0 and analyzed for Notch1 expression after 8 days of culture. Experiments of panels C, D, and F are representative of 2 experiments.