DNMT3A and acute myeloid leukemia: 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].