Fig. 3: Early seeding of RT.

a, Evolution of the RT subclone along the disease course based on WGS. Time lapse between the first and last sample analyzed (bottom). RT time points are marked in a rose color. Summary of the three patterns observed (right). b, Fish plot showing the clonal evolution along the course of the disease in patient 19 inferred from WGS analysis. Each subclone is depicted by a different color and number and its CCF is proportional to its height at each time point (vertical lines). Phylogeny of the subclones and main driver events (right). c, Mutation tree reconstructed by scDNA-seq for case 19 together with the fraction of cells carrying each specific combination of mutations in each time point. The total number of cells per sample is shown at the bottom. The number of cells assigned to each subclone is shown in Supplementary Table 20. d, Schematic representation of the clinical course and samples analyzed for patient 3,495 together with the size of the IGH subclones identified using high-coverage NGS analyses. Abbreviations for treatment regimens are detailed in Extended Data Fig. 1a. e, Clinical course and IGH subclones identified by DNA- and RNA-based NGS in patient 12. f, Uniform Manifold and Projection (UMAP) plot for case 12 based on the scRNA-seq data of all time points colored by annotation. g, Expression of key marker genes in each cluster identified in case 12. h, Distribution of cell-cycle phase scores for each cluster based on scRNA-seq in case 12. i, UMAP visualization split by time point in case 12 with the fraction of RT cells annotated. ‘n’, number of cells. j, Chromosomal alterations detected by WGS in chromosomes 1, 11 and 14 in CLL and RT samples of patient 12 (top). Copy number profile of RT cells detected at the different time points according to scRNA-seq. Only a subset of RT cells from time point 6 (time of diagnosis of RT) was included for illustrative purposes (bottom).