Fig. 1: LYN kinase in non-hematopoietic microenvironmental cells promoted CLL expansion.

a Graphical illustration of the in vivo experimental setup. I. Lyn^−/− mice were lethally irradiated and the hematopoietic system was reconstituted using Lyn^−/− or Lyn^wt/wt bone marrow transplantation (BMT), resulting in chimeric mice lacking LYN globally (tLyn^−/−) or specifically in the radioresistant stromal compartment (chLyn^-/-). II. The hematopoietic system was successfully reconstituted after 8 weeks and chimeric mice were subsequently transplanted with 10⁷ murine TCL1^tg/wt CLL cells (4 biological replicates). Illustration was created with BioRender.com. b Leukemic expansion in the peripheral blood was monitored every 14 days via flow cytometry and is displayed as fraction of CD5⁺CD19⁺ CLL cells in all CD45⁺ leukocytes (tLyn^−/− n = 7; chLyn^−/− n = 10; Lyn^wt/wt n = 8; mean ± SEM; two-sided Mann-Whitney test: Week 4 Lyn^wt/wt vs. chLyn^−/− p = 0.02499, Week 4 Lyn^wt/wt vs. tLyn^−/− p = 0.001166, Week 6 Lyn^wt/wt vs. tLyn^−/− p = 0.002165, Week 8 Lyn^wt/wt vs. tLyn^−/− p = 0.035714). c Kaplan-Meier curve illustrating the survival of chimeric recipient mice after CLL adoptive transfer (tLyn^−/− n = 6; chLyn^−/− n = 11; Lyn^wt/wt n = 8; Mantel-Cox log-rank test: Lyn^wt/wt vs. chLyn^−/− p = 0.0119, Lyn^wt/wt vs. tLyn^−/− p = 0.0021, chLyn^−/− vs. tLyn^−/− p = 0.4707). d Representative images of Hyperion Imaging Mass Cytometry of a healthy control lymph node (HC-LN) (top) and a CLL-LN (bottom). (Left) False color image (middle) result of cell-type segmentation (right) segmented fibroblasts color-coded by mean LYN intensity (bars represent 50 µm, representative of total n = 9 HC-LN and n = 12 CLL-LN). e Violin plot for mean LYN expression per segmented single cell (Healthy controls: n = 9 HC-LN (3272 endothelial cells; 6466 fibroblasts); CLL: n = 12 CLL-LN (1817 endothelial cells; 7543 fibroblasts); boxplots represent median with the interquartile range, whiskers indicate adjacent values, violin represents kernel density estimation, independent two-sided t-tests: endothelial p = 7.380e−41, fibroblasts p = 2.942e−170). See also Fig. S1. Source data are provided as a Source Data file.