(A) Clonal dynamics in the setting of therapeutic resistance. (B) WES of serial blood samples allows phylogenetic tree inferences, which highlight the presence of small subclonal populations driving relapse to ibrutinib therapy. (C) Clonal kinetics during ibrutinib treatment. Filled circles are measurements combining clonal fractions and absolute lymphocyte counts; empty circles are upper-bound estimates (1% of total CLL cells) for clones below the limit of detection; solid lines signify predicted kinetics for clones with 2 or more measurements; and dashed lines denote kinetics with minimal absolute growth rates for clones with only one measurement. (D) Droplet-based detection of resistance subclones at the time of treatment initiation. (E) Detection of RPS15-mutant specific single cells in pretreatment CLL samples as compared with a peripheral blood mononuclear cell control, using droplet-based single-cell detection. (F) Growth rates of relapsed CLL clones are several-fold higher than those of untreated CLLs.^1,64,65  Reprinted from Burger et al⁶⁴  with permission.