These include mutations in genes encoding transcription factors (e.g., RUNX1, CEBPA); those encoding signal transduction proteins such as FLT3, KIT and the RAS family of genes; genes involved in chromatin modification and epigenetic regulation including DNMT3A, IDH1/2, TET2 and ASXL1; genes of the spliceosome machinery (e.g., SRSF2, SF3B1, U2AF1) and genes encoding members of the cohesin complex (e.g., SMC3, SMC1A), as well as genes, such as NPM1, which is the most frequently mutated gene in AML, that cannot easily be assigned to any of these rather broad functional categories [7,27]. The gene discussed is DNMT3A; the disease is acute myeloid leukemia.