Compared to other driver mutations, DNMT3A and TET2 confer a lower risk of progression to AML, but additional mutations, as shown for example for Npm1 in mice, can drive CHIP to overt malignant transformation, and such genetic changes make diseases detectable years before diagnosis (Abelson et al., 2018; Loberg et al., 2019). This evidence concerns the gene DNMT3A and acute myeloid leukemia.