title: Panobinostat for the treatment of acute myelogenous leukemia.
abstract: BACKGROUND
  Therapeutic strategies in patients with acute myeloid leukemia (AML) have not changed significantly over the last decades. Appropriate strategies are ultimately driven by the assessment of patients' fitness to define suitability for intensive induction chemotherapy, which produces high initial remission rates but, increased likelihood of relapse. Old/unfit AML patients still represent an urgent and unmet therapeutic need. Epigenetic deregulation represents a strategic characteristic of AML pathophysiology whereby aberrant gene transcription provides an advantage to leukemic cell survival. Efforts to re-establish impaired epigenetic regulation include hypomethylating agents and histone deacetylase inhibitors (HDACi).
  
  
  METHODS
  The review discusses the underlying mechanisms leading to disruption of lysine acetyltransferases (KAT or HAT)/deacetylase (KDAC or HDAC) balance and the rationale for using the HDACi panobinostat (LBH-589) in AML.
  
  
  CONCLUSIONS
  Although panobinostat has produced significant results in myeloma, its efficacy remains limited in AML. Panobinostat exerts pleiotropic activity and lack of specificity, which likely contributes to its inadequate safety in elderly AML patients. Phase I-II trials, utilizing panobinostat associated with well-known chemotherapeutic agents are ongoing and combinations with other druggable targets may likely be evaluated in future trials. The clinical use of this HDACi in AML the near future does not appearing promising.
authors.affiliation: a Hematology Unit, Department of Onco-Hematology , A.O. of Cosenza , Cosenza , Italy.|b Biotechnology Research Unit , ASP of Cosenza , Aprigliano (CS) , Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.affiliation: c Department of Biomedicine and Prevention , Universita' Tor Vergata , Rome , Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.affiliation: d Department of Hematology , Universita' Cattolica S. Cuore , Rome , Italy.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohaus
authors.affiliation: a Hematology Unit, Department of Onco-Hematology , A.O. of Cosenza , Cosenza , Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: a Hematology Unit, Department of Onco-Hematology , A.O. of Cosenza , Cosenza , Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Vigna
authors.affiliation: b Biotechnology Research Unit , ASP of Cosenza , Aprigliano (CS) , Italy.
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.affiliation: e Department of Clinical and Experimental Medicine, Hematology Division , University of Pisa , Pisa , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Iovino
authors.affiliation: e Department of Clinical and Experimental Medicine, Hematology Division , University of Pisa , Pisa , Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Benedetti
authors.affiliation: c Department of Biomedicine and Prevention , Universita' Tor Vergata , Rome , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
authors.affiliation: e Department of Clinical and Experimental Medicine, Hematology Division , University of Pisa , Pisa , Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Galimberti
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D044127:Epigenesis, Genetic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D000077767:Panobinostat; D016896:Treatment Outcome
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D000077767:Panobinostat
keywords: NVP-LBH-589; Panobinostat; acute myeloid leukemia; high-risk myelodysplastic syndromes; histone deacetylase inhibitors; therapy