Approaches to studying clonal dynamics in CLL. (A) Serial blood draws coupled with volumetric measurements can help monitor CLL progression and contribute to estimations of growth kinetics. (B) Serial samples can increase the sensitivity of clonal detection as compared with depth of sequencing (reprinted from Gruber et al¹  with permission). (C) WES, mathematical modeling, and single-cell RNA sequencing can individually and in combination provide insight into determinants of clonal dynamics. Novel lineage-tracing tools are increasingly being leveraged to study clonal dynamics and evolution across cancers (left panel reprinted from Gruber et al¹  with permission; top right panel reprinted from Guieze et al⁶⁶  with permission; bottom right panel reprinted from Trapnell et al⁴⁴  with permission).