Clonal relationships between resistance mutations in CLL (n = 8 patients) and MCL (n = 1 patient) inferred from variant-based analysis of scDNAseq data. Clones are shown with their defining variants (ie, all detected nonsynonymous coding or splice variants, excluding germ line polymorphisms), clone size (percentage of analyzed cells), and number of cells. Clones with size <1.5% are indicated with a dashed circle. Zygosity of each variant is indicated (heterozygous [HET], homozygous [HOM], or hemizygous [HEM]), with the exception of BCL2, for which zygosity was not determined because of poor sequence quality (supplemental Figure 1). The BCL2 Val156Asp mutation detected in bulk sequencing data in patients CLL-G (at progression during venetoclax treatment) and MCL-A was not assessable on the scDNAseq panel, and MCL1 amplification was not assessable by bulk sequencing (patient CLL-G). Arrows indicate inferred clonal relationships (with the dashed arrow indicating a possible clonal relationship). Each clone was assessed for MCL1 copy number gain and TP53 copy number loss (CNL), and these are indicated when detected (supplemental Table 4; supplemental Figure 2). Clones harboring established or putative BCL2i and BTKi resistance mutations or both are indicated in red, blue, or purple, respectively. Myeloid clones (inferred by variant allele frequency analysis of samples taken at different time points containing little or no CLL disease) are indicated with gray text (patients CLL-B and CLL-F). BTK C481S mutations are followed by a suffix (a-d) to denote which nucleotide change was observed: a indicates NM_000061.2:c. 1441T>A; b, NM_000061.2:c.1442G>C; c, NM_000061.2:c.1442_1443delinsCT; and d, NM_000061.2:c.1440_1441delinsGA. Targeted agent exposure for each patient is shown (venetoclax [VEN], zanubrutinib [ZANU], or ibrutinib [IBR]).