DNMT1-depletion without cytotoxicity has therapeutic benefits even in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) containing p53-system defects102,105, and multiple clinical trials are ongoing to evaluate DNMT1-depletion more broadly in cancer therapy (although decitabine and 5-azacytidine used to deplete DNMT1 have pharmacologic limitations which can undermine their ability to deplete-DNMT1 from solid tumors) (Table 2). This evidence concerns the gene TP53 and acute myeloid leukemia.