Using variant allele frequencies to infer the chronological sequence of these events in leukemia development, it was shown that mutations in DNMT3A likely develop first in hematopoietic stem cells (or other mutations causing CH), followed by NPM1c second in a CMP, and FLT3 mutations (or RAS) third (Figure 3) [1,54,70]. This evidence concerns the gene DNMT3A and leukemia.