Fig. 1: Single-cell transcriptome atlas of T-PLL peripheral blood mononuclear cells.

A Experimental set-up of single-cell RNA sequencing in T-PLL: longitudinal peripheral blood sample pairs from 11 T-PLL patients were collected during indolent disease stage and after transition to active T-PLL. Additional unpaired samples were obtained from 5 indolent T-PLL patients and 1 active T-PLL². PBMCs were isolated and submitted to 3’ single-cell RNA sequencing. Publicly available data of 10 age- and sex-matched healthy donors⁷³ were integrated to create the final scRNA data set. PBMCs of 3 longitudinal sample pairs were additionally subjected to whole genome sequencing (WGS). Created in BioRender. Herling, M. (2026) https://BioRender.com/1mp0lnoB Exemplary tumor development of a primarily indolent T-PLL patient. White blood cell count (WBC) is illustrated over time. Samples were acquired at day 20 (indolent stage, blue) and day 874 (active stage, red) after diagnosis. C Comparison of established hematologic disease markers between indolent and active-stage T-PLL. WBC (mean 20.11 vs 120.57 G/l, indolent vs active T-PLL, p < 0.0001, Mann–Whitney–Wilcoxon test (MWW), two-sided) and serum lactate dehydrogenase (mean 236.7 vs 876.9 U/l, p < 0.0001, MWW, two-sided) were significantly increased in active T-PLL samples. Box plots: center: 50th percentile, box bounds: 25th and 75th percentiles (IQR), whiskers: smallest and largest observations within 1.5×IQR of the box. D t-SNE representation of batch-corrected PBMC single-cell gene expression data. Cell colors indicate the sample of origin. E t-SNE representation of PBMC data sets color-coded by type of sample (gray: healthy donor, blue: indolent T-PLL, red: active T-PLL). F Single-cell expression of T-PLL marker genes in the PBMC data set¹⁹. Colors indicate relative gene expression (light gray: minimal observed expression, red: maximum observed expression). G t-SNE projection of unsupervised-predicted cell type labels in the PBMC data set. Colors represent the assigned major cell types. H Relative contribution of different cell types (color-coded, see (G)) among samples. Letters on the right y-axis indicate the type of sample (H: healthy donor, I: indolent T-PLL sample, A: active T-PLL sample). I Dot plot visualization of hematologic marker gene expression among different cell types. Dot colors indicate scaled normalized expression values (blue: low relative expression, red: high relative expression). Dot sizes represent the percentage of cells within each cell type expressing the respective gene. Source data and complete summaries of statistical analyses are provided in the Source Data file.