Figure 2: ctDNA detects clonal evolution in CLL patients with RS.

(a) Graphical representation of the linear pattern of evolution of CLL to RS in CLL004 revealed by LC-WGS of the plasma and WES of plasma (P) and BM/LN. (b) Depth of coverage (DOC) log₂ ratio plots from LC-WGS of plasma in CLL004 at baseline (top panel) and at RS (bottom panel) showing CNAs specific to the dominant CLL clone in yellow and new CNAs at the time of RS in blue. (c) Heat-map illustrating the distribution of predicted functional SNVs from WES at baseline (BM and P) and at progression to RS (LN and P shown in red) in CLL004. (d) Graphical representation of the linear pattern of evolution of CLL to RS in CLL054. (e) DOC log₂ ratio plots from LC-WGS of plasma in patient CLL054 at baseline (top) and at RS (bottom) showing CNAs specific to the dominant CLL clone (yellow) and new CNAs at the time of RS (blue). (f) Heat-map illustrating the distribution of predicted functional SNVs from WES at baseline (PB and P) and at progression to RS (BM, LN and P shown in red) in CLL054. (g) Graphical representation of the branched pattern of evolution of CLL to RS in CLL022. (h) DOC log₂ ratio plots from LC-WGS of plasma in CLL022 at baseline (top) and at RS (bottom) showing CNAs specific to the ancestral CLL clone (yellow), the dominant CLL clone (green) and new CNAs at the time of RS (blue). (i) ctDNA levels in CLL022 showed a decrease in the TP53 p.R248Q mutation post venetoclax treatment. In contrast, there was an increasing fractional abundance of TP53 p.C238S and SF3B1 p.K666M mutations observed in the plasma as the patient progressed to RS. These mutations were detected in plasma 64 days before the clinical diagnosis of RS. (j) Heat-map illustrating the distribution of predicted functional SNVs from WES at baseline (BM and P) and at progression to RS (BM and P shown in red) in CLL022.