NPM1 and acute myeloid leukemia: Importantly, in AML, the LSCs arise when these mutations are acquired—in a stepwise manner—in genes that control HSCs’ (i) quiescence and proliferation (FLT3, RAS, P53, c-KIT, and STAT3), (ii) self-renewal and differentiation (NPM1, RUNX1, CEBPA and other myeloid transcription factors), and (iii) epigenetic regulation (DNMT3A, DNMT3B, DNMT1, TET1, TET2, IDH1, IDH2) [28,29,30] (Figure 2A).