title: Lost in translation? Ten years of development of histone deacetylase inhibitors in acute myeloid leukemia and myelodysplastic syndromes.
abstract: BACKGROUND
  Epigenetic changes and mutations in epigenetic modifiers characterize and likely drive many cases of acute myeloid leukemia and myelodysplastic syndrome. Development of DNA methyltransferase inhibitors has been most successful in these diseases. While many epigenetic marks are potential targets of cancer therapies, histone deacetylase inhibitors (HDACi) have undergone the most advanced development to date.
  
  
  METHODS
  In this review, the authors describe and discuss the biology and the clinical results of HDAC inhibitors in the settings of myeloid malignancies.
  
  
  CONCLUSIONS
  While significant results have been achieved in lymphoma and myeloma, efficacy remains limited in myeloid malignancies for both single agent and HDACi based combination regimens. The redundancy and the pleiotropic activity of HDACi (on both histone and non-histone proteins) are key factors that have limited to date the selection of patients and the design of robust biomarkers. Recent advances in biology (mechanisms of resistance, immunology) and the design of a more specific third generation of HDACi are two important features that will drive the future clinical development of HDACi in myeloid malignancies.
authors.affiliation: a Department of Internal Medicine , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stahl
authors.affiliation: b Department of Internal Medicine, Section of Hematology , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gore
authors.affiliation: c Hematology Department , Institut Paoli-Calmettes and Aix-Marseille Université , Marseille , France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: b Department of Internal Medicine, Section of Hematology , Yale University School of Medicine , New Haven , CT , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018579:Patient Selection
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors
keywords: AML; Epigenetics; HDACi; HDACi based combination therapy; Histone deacetylase inhibitors; Hypomethylating agents; Immunotherapy; MDS; Vorinostat; myeloid malignancies