Aberrant recruitment of histone deacetylase complexes by oncoproteins such as AML1–ETO and PML–RARA enforces chromatin compaction at promoters of tumor-suppressor and differentiation-related genes, thereby preserving oncogenic transcriptional programs, preventing normal myeloid maturation, and fostering chemotherapeutic resistance in AML. The gene discussed is PML; the disease is acute myeloid leukemia.