title: The DAC system and associations with acute leukemias and myelodysplastic syndromes.
abstract: Imbalances of histone acetyltransferase (HAT) and deacetylase activity (DAC) that result in deregulated gene expression are commonly observed in leukemias. These alterations provide the basis for novel therapeutic approaches that target the epigenetic mechanisms implicated in leukemogenesis. As the acetylation status of histones has been linked to transcriptional regulation of genes involved particularly in differentiation and apoptosis, DAC inhibitors (DACi) have attracted considerable attention for treatment of hematologic malignancies. DACi encompass a structurally diverse family of compounds that are being explored as single agents as well as in combination with chemotherapeutic drugs, small molecule inhibitors of signaling pathways and hypomethylating agents. While DACi have shown clear evidence of activity in acute myeloid leukemia, myelodysplastic syndromes and lymphoid malignancies, their precise role in treatment of these different entities remain to be elucidated. Successful development of these compounds as elements of novel targeted treatment strategies for leukemia will require that clinical studies be performed in conjunction with translational research including efforts to identify predictive biomarkers.
authors.affiliation: Medizinische Klinik II, Abteilung für Hämatologie und Onkologie der, Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004354:Drug Screening Assays, Antitumor; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000201:enzymology*; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D056572:Histone Deacetylase Inhibitors; D014212:Tretinoin; D006655:Histone Deacetylases