Extended Data Fig. 9: B-ALL developmental states are associated with clinical outcomes.
a-d) Association between age at diagnosis and inferred abundance of HSC/MPP (a), myeloid progenitor (b), pre-pDC (c) and pre-B developmental states (d). For each association, the LOESS regression line shaded with the 95% CI is shown for 2,019 B-ALL with available age information. e-h) Association between developmental state abundance and clinical characteristics in B-ALL. 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. e) Association between B-ALL clinical risk groups and inferred abundance of HSC/MPP, myeloid progenitor, and pre-pDC developmental states among 2,022 B-ALL patients annotated for clinical risk (childhood high risk, HR, n = 680; childhood standard risk, SR, n = 527; AYA, n = 430; adult, n = 385). f,g) Association between measurable residual disease (MRD) status at day 29 of induction and inferred abundance of indicated developmental states (f) as well as of early lymphoid, pro-B and pre-B developmental states (g) at diagnosis (n = 1,197 pediatric patients with MRD status (Negative < 0.01%, n = 787; Positive > 0.01%, n = 410). h) Association between MRD levels at day 29 and inferred developmental state abundance at diagnosis (n = 794 pediatric B-ALL patients with MRD levels available: < 0.01%, n = 448; 0.01–0.1%, n = 148; 0.1–1%, n = 104; 1–10%, n = 54). i-k) Association of B-ALL developmental states with survival outcomes across different subsets of B-ALL patients. Hazard ratios from univariate cox regression, or multivariable cox regression when indicated, related to OS and EFS are reported for each standard deviation increase in inferred abundance. Error bars depict the 95% confidence interval for each variable of interest, presented as the hazard ratio ±− 1.96 standard errors. i,j) For each developmental state and multipotency score, association with survival outcomes is performed within 1,039 pediatric B-ALL patients (i) and within 649 pediatric B-ALL patients with negative MRD (j). COG, Children's Oncology Group. k) Association of B-ALL developmental states with survival outcomes within genetically diverse adult B-ALL patients. ECOG-ACRIN, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group. Hazard ratios for overall survival and event-free survival from univariate Cox regression (n = 324 for each developmental state/multipotency score, left panel) or adjusted hazard ratios (n = 312 for each developmental state/multipotency score, right panel) from multivariable Cox regression accounting for age, sex, WBC, genomic and clinical risk group as independent covariates are reported for each standard deviation increase in inferred abundance.
