Distinct clinical characteristics of the DUX4 subtype. (A) Patients with the DUX4 subtype have higher day-33 MRD. (B) In MS2003, patients with the DUX4 subtype had significantly poorer day-8 PB response than patients in MS2010, which used IV vincristine. CIR (C) and OS (D) of DUX4 subtype compared with conventional LR subtypes (including ETV6-RUNX1 and high hyperdiploid) and HR subtypes (including BCR-ABL1, KMT2A, hypodiploid, and near haploid). (E) Relationship between ERG deletion and DUX4 subtype. (F) Patients with the ERG deletion in the DUX4 subtype had better day-33 MRD. (G) Unsupervised hierarchical clustering of the DUX4 subtype showing that ERG deletions are associated with distinct gene expression signatures. Genes with significantly higher variance in DUX4 subtypes than the rest of the cohort (by Conover squared ranks test) with adjusted P value (by Holm’s method) <.05 were first selected. In the selected genes, the top 200 genes with the highest median absolute deviation in DUX4 subtype were used in hierarchical clustering using correlation coefficient as the distance metric and Ward’s algorithm.