NPM1 and acute myeloid leukemia: The first category corresponds to the successive occurrence of a mutation in a gene coding for epigenetic regulation, including DNA methylation (DNMT3A and TET2), followed by a mutation in NPM1 or in a classically-mutated transcription factor in AML (RUNX1, CEBPA, and GATA2), then the last mutation arises in a gene involved in the signaling pathways (FLT3, RAS, KIT or other TK/RAS pathway genes) [11].