Notably, in DNMT3A, variants at the p.R882 hotspot codon were less common in CH (4/87 DNMT3A mutations, 5%) compared to MDS (9/28, 32%) and sAML (14/37, 38%) (p < 0.001) (Fig. 7), suggesting that codon p.R882 mutations associate with disease progression and may have different functional implications compared to other variants in the gene. This evidence concerns the gene DNMT3A and cyclic hematopoiesis.