Novel insights into CLL based on single-cell analysis. (A) Bulk analysis of heterogeneous tumor samples, including those admixed with immune and stromal cells, provides useful global gene expression data but results in loss of granularity. Single-cell approaches allow analysis within individual cells as well as in similar cell populations that have clustered to identify unique signatures, cellular processes, networks, and rare cell populations, which provides higher resolution biological insights. (B) Single-cell mutational analysis can yield detailed phylogenetic trees to identify which mutations occur in specific unique subclones and which track together. In this example, multiple sCNA and sSNV were interrogated by using targeted sequencing to establish the underlying clonal architecture of the leukemia. This demonstrated convergent loss of TP53 with 17p deletion in 1 subclone and TP53 mutation in another, which was further corroborated by conventional FISH analysis by Wang et al.⁵⁰