Distinct subsets of clonal cytopenia of undetermined significance segregated by unsupervised clustering and clone metrics. (A) Distribution of VAF of the subsets of CCUS, according to the unsupervised analysis: CH-like cluster (green); and MN with myelodysplasia (MDS)-like subset (orange). (B) Distribution of VAFs of the subsets of CCUS recognized within the MN-like cluster based on clone metrics: MN-like subset characterized by patterns with high clinical expressivity (blue); MN-like subset characterized by mutation patterns with low clinical expressivity (maroon); MN-like subset characterized by isolated TET2, ASXL1, or less frequently mutated genes (gray). (C) Cumulative incidence of progression to MN estimated with a competing risk approach in CCUS subsets segregated based on unsupervised analysis and clone metrics (CH-like cluster, [green curve]; MN-like subset driven by isolated TET2, ASXL1, or less frequently mutated genes [gray curve]; subset with MN-like patterns with high clinical expressivity [orange curve]; and subset with MN-like patterns with low clinical expressivity [maroon curve]). Overall, 25 patients with CCUS progressed to MN, accounting for 0%, 17%, 27%, and 55% of the CH-like cluster, MN-like subset driven by isolated TET2, ASXL1 or less frequently mutated genes, MN-like subset with high clinical expressivity, and MN-like subset with low clinical expressivity, respectively.