title: Genetic mutations in epigenetic modifiers as therapeutic targets in acute myeloid leukemia.
abstract: BACKGROUND
  Despite enormous insights into the molecular mechanisms of acute myeloid leukemia (AML) pathophysiology, this disease is still fatal in the majority of patients, highlighting the urgent need for novel biomarkers useful in AML prognosis and therapy.
  
  
  METHODS
  The advent of modern sequencing technologies has allowed the identification of genetic mutations in genes encoding for specific enzymes involved in the epigenetic regulation of gene expression. The authors review recent data demonstrating the involvement of mutations in genes encoding for epigenetic players and their complex combination with somatic genetic mutations in the pathogenesis of AML. They also discuss the prognostic and therapeutic implications of these findings.
  
  
  CONCLUSIONS
  Current clinical and preclinical studies are underscoring the importance of targeting epigenetic modifiers as new biomarkers for a better prognostic risk stratification and therapeutic evaluation of intermediate-risk patients. Combining data from traditional and modern methodologies will allow a definition of the complex networks of epigenetic changes and molecular interactions between candidate epitargets and key regulators of hematopoiesis. It will thus be possible to achieve an overview of potential aberrant mechanisms driving leukemogenesis in different classes of AML patients. Such an improved approach could pave the way towards 'personalized' therapies.
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples , Via L. De Crecchio 7, 80138 Naples , Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.forename: Rosaria
authors.initials: R
authors.lastname: Benedetti
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Conte
authors.forename: Concetta
authors.initials: C
authors.lastname: Iside
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009154:Mutation; D057285:Precision Medicine / Q000379:methods; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: acute myeloid leukemia; clinical trials; epidrugs; epigenetic modifiers; mutation; therapy