These localized changes in the bone marrow microenvironment (BMME) explain why traditional therapies for MDS/AML, including chemotherapeutics and hypomethylating agents, are not as effective in <i>TP53</i>-mutated myeloid neoplasms and demonstrate the dire need for new treatments in this patient population. The gene discussed is TP53; the disease is acute myeloid leukemia.