Profound immunosuppression mediated by myeloid-derived suppressor cells, the upregulation of cytokines and cell-surface receptors on leukemic cells, the suppression of native immune regulator cells, and metabolic aberrations in the bone marrow are features of the <i>TP53</i>-mutated AML/MDS marrow microenvironment. The gene discussed is TP53; the disease is acute myeloid leukemia.