NPM1 and acute myeloid leukemia: Mutations in exon 12 result in cytoplasmic localization of the protein, implicating NPM1 in leukemogenesis through diverse mechanisms.3,4 NPM1 mutations drive AML in one-third of cases.4 They often stem from preexisting clonal hematopoiesis.4-6 DNMT3A mutations are considered early molecular events responsible for preceding clonal hematopoiesis.