Application of single-cell technology to CLL. CLL is present within blood, lymph nodes, and bone marrow where it coexists with a range of immune and stromal cells that are central to disease pathogenesis. Analysis of CLL may focus uniquely on leukemia cells, supporting cells, or both from all 3 distinct tissue compartments. A range of established and developing single-cell techniques characterizing the genome, transcriptome, and proteome have been developed to allow enhanced appreciation of CLL biology. Ab, antibody; lncRNA, long non-coding RNA; miRNA, microRNA; NK, natural killer; scRRBS, single-cell reduced representation bisulfite sequencing; seq, sequencing; WES, whole-exome sequencing; WGS, whole-genome sequencing.