Interestingly, DNMT3A mutations were consistently documented in primary and relapse samples from all the 5 cases with NPM1 mutation loss at relapse, suggesting that DNMT3A mutation most likely preceded NPM1 mutation in the pathogenesis of the disease and a common ancestral DNMT3A-mutated clone with NPM1 wild-type gave rise to both primary and relapsed AML [95]. This evidence concerns the gene NPM1 and acute myeloid leukemia.