Transcriptomic and genomic landscape of DS-ALL. (A) Subtype classification of 295 DS-ALL cases with available RNA-Seq or paired tumor-germline WGS data. Each column represents a patient, and each row represents a feature, including sex, age, availability of data, rearrangements, and expression of CRLF2, CEBPD, and IGF2BP1. The patients are ordered according to subtypes. In 2 cases with CEBPD overexpression, chromosomal rearrangements of CEBPD locus to intergenic regions of 9p13.2 (between PAX5 and ZCCHC7) and 6q25.3 (∼380 kb upstream ARID1B) were identified. As no fusion transcript was identified by RNA-Seq, these rearrangements are denoted as 9p13.2::CEBPD and 6q25.3::CEBPD. (B) Gene expression of 249 DS-ALL cases visualized by UMAP. Top 100 genes with the highest median absolute deviation were used to generate this 2-dimensional UMAP. Subtypes are shown in different colors. (C) Genomic alterations in 244 DS-ALL cases. The cases are ordered by subtypes, as indicated above the panel. Only genes significantly altered in DS-ALL are included.