Fig. 6: Senescence-associated myeloid skewing links novel DLBCL subtypes to favorable outcomes.

a Average expression scores of “dendritic cell (DC) vs. B cell up” (DC score, top) and “PU.1 targets in TIS” (PU.1[TIS] score, bottom [cf. Supplementary Data 5]) signatures in subgroups of the Duke diffuse large B-cell lymphoma (DLBCL) cohort⁶⁸ classified into the indicated lymphoma ecotypes (LE; n as indicated in the figure)⁷⁶. * marks ecotypes with significantly higher scores than at least half of the other LE groups (Benjamini-Hochberg adjusted P < 0.05, see Source Data for the exact P-values for each pairwise comparison), as assessed by pairwise two-sided Wilcoxon rank-sum test; LEs marked high for both gene signatures are depicted in bold. “Uncl.” denotes unclassified cases. b River plot showing dynamic changes of the gene expression profile (GEP)-based LE designation between matched pairs of untreated (UT) and 4-hr cyclophosphamide (CTX)-in vivo-challenged Eμ-myc lymphomas (GSE134751; n = 37 each). Only LE classifications with at least three samples were considered (hence, LE4 was excluded). Pearson’s χ² P value is displayed. c Gene set enrichment analysis comparing GEP of lymphomas that formed from Eμ-myc transgenic hematopoietic stem cells with or without stable introduction of a MyD88-L265P lesion in recipient mice (n = 7 each; GSE141454⁶). Positive normalized enrichment scores (NES) signify enrichment in MyD88-L265P⁺ lymphomas. Gene sets scoring with false discovery rate (FDR) < 0.05 are marked gray. d Kaplan-Meier plot of overall survival and log-rank P value in the Duke cohort stratified as in Fig. 5g, but selected for patients with a MyD88 mutation (DC^high, n = 51 vs. DC^low, n = 66). e GEP of DLBCL patients as in d, scored for the average expression of the core SUVARness senescence signature³⁹ (left), and the PU.1(TIS) signature (right). P-values by two-sided Wilcoxon rank-sum test. a, e Box plots show the median as center line, 25% and 75% percentiles as box limits, and whiskers extending to largest and smallest values within the 1.5× interquartile range of the box limits. Source data are provided in the Source Data file.