Future directions for single-cell technology in CLL. Sampling from various compartments such as the blood, lymph nodes, and bone marrow (A) and sampling from early stages of the CLL disease (B) can increase our understanding of CLL development and may aid with earlier diagnosis and treatment optimization. Additionally, using a variety of high-throughput methods such as multiome profiling (C) and spatial analysis (D) can provide an in-depth understanding of CLL and immune cell regulation and function. (E) In the future, single-cell analysis potentially could inform clinical diagnostics for early disease detection, early detection of relapse, and evaluation of the functional state and potential therapeutic vulnerabilities of the relapsed cells. HSC, hematopoietic stem cell.