Longitudinal overview of somatic variants observed in CLL-associated genes in 4 patients during the early stages of MBL/CLL development. Only patients with samples likely to constitute a low-count MBL clone are shown (initial sample ranging from 16 to 8.4 years before CLL diagnosis). Each sample is depicted as an MBL/CLL clone for which variants present are indicated alongside the VAF, with variants with a VAF below 1% depicted as <1%. Low-frequency variants (<3%) are only shown if validated through ddPCR. Each sample is labeled with the dominant clonotype frequency (Freq.) as determined through NGS amplicon sequencing of the IGH gene repertoire. X-axis denotes time at which each blood sample was drawn in years before diagnosis. ∗Notably, NOTCH1 and XPO1 variants observed in biclonal CLL patient 2 (indicated with an asterisk) were annotated next to the expanding CLL clone corresponding with the expansion of these variants over time to diagnosis, although formally, we are not able to exclude the possibility that these variants could be present in the other CLL clone in this patient. Stereotypic subsets are indicated for the relevant patients. Cytogenetic aberrations observed at diagnosis are shown when available. The 8 other patients for whom no somatic variants were observed are not included in this graphic.