Patient samples and experimental design. (A) Swimmer plot of each patient from the time of diagnosis to last follow-up or death. Diagnosis of CLL or small lymphocytic lymphoma and timing of sample collection and treatment initiation are shown. Some patients had not received the first treatment at the last follow-up. The types of sequencing performed on PB and LN samples are indicated on the left. (B) Illustration of the types of sequencing performed: (1) bulk RNA-seq (n = 29); (2) WES (n = 14) of CD19⁺ tumor cells from paired PB and LN samples; (3) scRNA-seq of paired PB and LN samples (n = 5); (4) bulk RNA-seq of unsorted CLL LN samples (n = 34); and (5) bulk RNA-seq of unsorted normal LN samples (n = 4).