NPM1 and acute myeloid leukemia: For instance, the typical CHIP-derived hierarchy of AML comprises early lesions in DNMT3A, TET2 and ASXL1 that aggregate together or with other mutations in epigenetic regulators, followed by mutations in NPM1 or in haematopoietic transcription factors, and then by lesions in signalling pathways such as FLT3 and RAS.