For therapy-related myelodysplastic syndromes after curative treatment of NPM1-mutant AML it has been demonstrated that there can be pre-existing or even newly developed clonal pre-leukemic hematopoiesis, concomitantly with the acquisition of new somatic alterations (such as DNMT3A, IDH1/2 and TET2 mutations) [49]. Here, NPM1 is linked to acute myeloid leukemia.