TetIL-7R tumors display hyperactivation of the PI3K/Akt pathway and mimic multiple features of human T-ALL. (A) Hierarchical clustering analysis of Pearson correlation coefficients between mouse tumors and human T-ALL. Each row corresponds to a mouse leukemia and each lane to a human T-ALL sample. Transcriptomic analyses showed that mouse tumors resemble either TAL/LMO+proliferative T-ALLs (cluster 1) or HOXA/TLX+immature (cluster 2), as defined in Homminga et al.³¹ Robustness of this analysis is shown by the fact that mouse leukemias that were “classified” as HOXA/TLX+immature–like display features of immature/ETP-ALL, such as higher KIT, CD33, and CD34 than the other tumors (supplemental Figure 4). (B) Akt activation (p-Akt), and PTEN and p27^Kip1 expression levels were evaluated by immunoblot in On-dox F5 TetIL-7R thymic tumors (T-ALLs) vs control thymic samples from healthy, F5 mice (Ctrls). (C-G) GSEA of the ranked expression differences between tumors and controls for the KEGG pathways: phosphatidylinositol signaling (C), mTOR signaling (D), JAK-STAT signaling (E), Notch signaling (F), and cell cycle (G). (H) Bcl-2 expression levels were evaluated by immunoblot in tumors and controls. KEGG, Kyoto Encyclopedia of Genes and Genomes.