Transcriptome and methylome profiles of established mouse models recapitulating human leukemia. (A) Unsupervised hierarchical clustering identified 2 main gene expression subgroups associated with leukemia phenotype. Group 1 included samples with combinations of CRISPR/Cas9–induced mutations in Trp53, Bcor, Dnmt3a, Nfix, Tet2, or Rb1 and samples with NTRK1/TP53 double mutations. Color legends are the same in panel B. (B) Heatmap of NetBID-inferred activity of top 34 positive and 41 negative TF drivers in the comparison of AEL mouse model vs other leukemia subtypes (N = 75, and the P < 1e-9 was used as the significance cutoff). Drivers in the top 34 rows are upregulated in the AEL mouse model, whereas the bottom 41 rows represent genes downregulated in the AEL mouse model. Sample order is the same from panel A. (C) Gene set enrichment analysis confirmed that the established mouse AEL models recapitulated human AEL.¹⁰  (D) Heatmap of beta values, with 0 for unmethylated CpGs in light blue, and 1 for methylated CpGs in orange. Top 8000 most variable CpGs were selected based on mean absolute deviation score of M-value (log₂Ratio) and used for hierarchical clustering. Three main groups were depicted that were correlated with genotype and gene expression profile. Each color represents a different leukemia model. Color legends for subtypes, passages, and mutations are from panels A and B. FDR, false discovery rate; Pri_mouse, primary mouse ID; RNA-seq HC, RNA-seq hierarchical clustering.