Fig. 4: TIS-associated gain of aberrant myeloid features in DLBCL cell line models.

a, b Senescence-associated β-galactosidase (SA-β-gal) and nitroblue-tetrazolium (NBT) respiratory burst staining of SU-DHL10 cells (senescence-competent) after 5-day adriamycin (ADR) exposure or left untreated (UT) (top; mean percentage of positive cells ± SD from n = 3 independent experiments). Scale bars, 100 μm. Quantification of SA-β-gal and NBT in DLBCL cell lines categorized as senescence-competent, -intermediate or -incompetent (bottom; n = 6 each). See Supplementary Data 4 for the group designation. c Mean percentage ± SD of surface CD11c⁺CD20⁺ on SU-DHL10 cells as in a, b (top). CD11c mean fluorescence intensity (MFI) difference between ADR-treated and UT cells across cell lines as in a (bottom). a–c Bars show mean percentage of positive cells ± SEM (a, b) or ΔMFI ± SEM (c), except for acute monocytic leukemia cell line THP-1 as positive control (b): ± SD (n = 4 independent measurements). Two-sided P-values by paired t-test for UT vs. ADR comparisons within same category, by unpaired t-test between categories. d DoRothEA TF footprinting of DLBCL cell line RNA-seq comparing 5-day ADR-treated, cell-cycle arrest-enriched to UT, proliferation-enriched cells. Top 50 TF shifting activity comparing senescence-competent to -incompetent groups (n = 6 cell lines each) with normalized enrichment scores (NES) reflecting treatment-induced relative gain (red) or loss (blue) of TF activity. e Proliferation of Karpas-422 cells expressing PU.1-ER^T2, C/EBPβ-ER^T2, JUN-ER^T2 or empty vector, and 5-day exposed to ADR and/or 4-hydroxytamoxifen (4-OHT), or solvent (UT). Cell numbers as mean fold-change ± SD (top) and SA-β-gal in matching samples as mean percentage of positive cells ± SD (bottom). n = 4 independent experiments. f Percentage of CD11c⁺ cells by flow cytometry of cells as in e, except n = 3 for C/EBPβ-ER^T2. e, f P-values by two-sided, paired t-test. g Heatmap of qRT-PCR-based relative transcript abundance of cells as in (e). Transcripts are categorized as indicated; senescence-associated secretory phenotype (SASP), antigen-presenting cell (APC). Row Z-scores of fold-change geometric means compared to untreated, empty vector from n = 3 independent experiments. Gray indicates transcript levels below detection. IL1B, CCL22, IL6, and CD44 fold-changes were log₂ transformed prior to Z-scoring. Source data are provided in the Source Data file.