Proximity to more immature lymphopoiesis stages defines multilineage BCR::ABL1-positive ALL, which has a similar outcome as lymphoid BCR::ABL1-positive ALL. (A) Differential gene expression analysis between multilineage and lymphoid BCR::ABL1-positive ALL was performed using 1-way analysis of variance (supplemental Table 7). The 100 most significantly differentially expressed genes were used for hierarchical clustering of BCR::ABL1-positive samples (upper panel). The expression heat map in the lower panel shows gene expression of the same genes in healthy B-cell progenitors.¹⁵ (B) ALLCatchR¹⁵ single-sample enrichment scores²⁰ for samples from the 4 subclusters are shown using gene set definitions of normal B lymphopoiesis. (C-D) Uniform manifold approximation and projection (UMAP) plots showing gene expression data of 2567 patients with BCP-ALL, previously aggregated from 3 cohorts¹⁵ and including now the 2 major (C) and 4 subcluster (D) BCR::ABL1 groups. The UMAP plots are based on the 3058 genes defined for BCP-ALL subtypes¹⁵ and BCR::ABL1 clusters. The updated version of ALLCatchR, providing molecular subtype allocation to BCP-ALL subtypes, including the novel BCR::ABL1 clusters, is available online (https://github.com/ThomasBeder/ALLCatchR_bcrabl1). (E) The distribution of age groups (upper left), BCR::ABL1 break points (lower left), and white blood cell counts (WBC, upper right) at initial diagnosis are shown for subclusters of the aggregated data set. The solid line in the dot plot showing WBC distribution represents a WBC of 30 000/μL, and red diamonds are the medians. Corresponding data and statistical analyses are provided in supplemental Tables 1,13, and 14. (F-H) DFS recorded at a median of 3 years for 91 GMALL BCR::ABL1-positive patients treated according to GMALL protocols with dose-reduced chemotherapy induction combined with imatinib, followed by consolidation I with continuous imatinib treatment and indication for allogeneic stem cell transplantation in first complete remission is shown. Kaplan-Meier analysis was used to calculate survival probabilities, and differences were assessed by log-rank test.