In this review, we will outline a picture of the most frequently mutated tumor suppressor genes in AML, such as IDH1, IDH2, TET2, DNMT3A and WT1 (Table 2), NPM1, CEBPA and TP53 (Table 3) (Table 2 and Table 3), as well as others recently discovered to be involved in the disease with a lower mutation frequency, including EZH2, GATA2, splicing factors and miRNAs (Figure 1). This evidence concerns the gene NPM1 and acute myeloid leukemia.