Extended Data Fig. 7: B-ALL developmental states refine existing genomic subtypes.
a-c) Association between genetic alterations and multipotency score or inferred abundance of B-ALL developmental states from patients with DUX4-R (a), KMT2A-R (b) and BCR::ABL1 (c) B-ALL. The magnitude of each association, quantified as the –log10 (P value), is depicted through the size and color intensity of each dot. The direction of the association is depicted through the color, wherein higher abundance is green and lower abundance is purple. Only associations with an unadjusted P < 0.05 are depicted, with a star denoting at FDR < 0.05. Within each subtype, samples with each alteration were compared against all other samples. BCR::ABL1 transcript type (p190, p210) is not shown in (c) due to a lack of significant associations at P < 0.05. d) Violin plot of the AUCell enrichment scores for the four indicated DUX4-R subtype-level cNMF metaprograms. e) GSEA on the genes from (d) ranked by their contribution to Differentiation and Inflammation programs in DUX4-R transcriptional subgroups. f) Violin plots of gene expression pattern for twelve selected genes in 10 DUX4-R patients. g) Scatter dot plots of CD44 (left) and CD10 (right) protein expression by flow cytometric analysis in DUX4-R early/multipotent (n = 6) and DUX4-R Committed (n = 4) B-ALL samples. Two-tailed P value is from unpaired t test. Each point in the scatter plot represents individual samples. The bar plot represents the mean with error bars indicating the standard deviation. h) KMT2A gene fusion partners in Early/Multipotent and Committed KMT2A-R subgroups. i) Association between KMT2A fusion partner and multipotency score or developmental state abundance. KMT2A fusion partners (AFF1, n = 93; EPS15, n = 4; MLLT1, n = 19; MLLT3, n = 11; MLLT10, n = 10) harbored by patients within each KMT2A-R subgroup are shown alongside the inferred abundance of early lymphoid, myeloid progenitor and pre-B states. For each comparison, P values from a two-tailed Wilcoxon rank-sum test are reported. Box plots indicate the range of the central 50% of the data, with the central line marking the median. Whiskers extend from each box to 1.5x the interquartile range. j) Oncoprint showing co-lesions in pediatric BCR::ABL1 patients for which both SNVs/indels and bulk RNA-seq data were available (BCR::ABL1 early/multipotent, n = 9; BCR::ABL1 inter-pro, n = 6; BCR::ABL1 committed, n = 28. Only significant P values from Fisher's exact test of early/multipotent versus committed are shown.
