TP53 mutations, which are found in 5–10% of de novo AML and up to 30–40% of therapy-related and secondary AML, represent a significant challenge in AML and MDS due to their resistance to conventional chemotherapy, including cytarabine- and anthracycline-based chemotherapy [68,72,73,74]. The gene discussed is TP53; the disease is myelodysplastic syndrome.