NPM1 and acute myeloid leukemia: It has been suggested that AML arises from three complementary classes of mutation (46,47): class I mutations in tyrosine kinases including FLT3; class II mutations in transcription factors including RUNX1, CEBPA and NPM1; class III mutations in genes associated with DNA methylation including DNMT3A; and, another class associated with tumor suppressor mutations.