Heterogeneity of CRLF2-r DS-ALL. (A) Unsupervised hierarchical clustering of 130 CRLF2-r DS-ALL samples with RNA-Seq data identified a unique group of cases with BCR::ABL1-like gene expression signatures. BCR::ABL1-like classification by PAM based on non–DS-ALL data is indicated by red bars above the heatmap. (B) Projecting the BCR::ABL1-like and non–BCR::ABL1-like CRLF2-r subtypes to UMAP shows that BCR::ABL1-like CRLF2-r cases cocluster with BCR::ABL1 and non-CRLF2-r BCR::ABL1-like, and are distinct from non–BCR::ABL1-like CRLF2-r. (C) Genomic alterations in BCR::ABL1-like and non–BCR::ABL1-like CRLF2-r subgroups. Genes altered in >6% of CRLF2-r DS-ALL are shown.