title: Inhibitors of LSD1 as a potential therapy for acute myeloid leukemia.
abstract: BACKGROUND
  Epigenetic dysregulation plays a critical role in the pathogenesis of acute myeloid leukemia (AML). Alterations in histone methylation lead to aberrant silencing of expression of multiple genes involved in tumor suppression and cell cycling, resulting in myeloid maturation arrest and proliferation of early myeloid progenitors. One promising approach targeting chromatin regulatory proteins is inhibition of lysine specific demethylase-1 (LSD1), an enzyme responsible for demethylation of histone H3 as well as other functions
  
  
  METHODS
  Available literature on LSD1 in normal and malignant hematopoiesis was identified in PubMed and reviewed. Areas addressed here include the biology of LSD1, pharmacologic inhibitors, and preclinical data supporting the rationale for LSD1 inhibition in AML therapy.
  
  
  CONCLUSIONS
  LSD1 inhibitors represent a promising novel epigenetic approach for AML therapy. Preclinical studies have revealed that pharmacologic LD1 inhibitors function primarily by altering stem cell programs and restoring myeloid differentiation to AML cells. These effects are markedly enhanced in combination with trans-retinoic acid or histone deacetylase inhibitors with little toxicity. Currently, multiple oral LSD1 inhibitors are undergoing phase 1 investigation in patients with AML. The results of these clinical trials are eagerly awaited.
authors.affiliation: a Department of Medicine , Roswell Park Cancer Institute , Elm and Carlton Streets, Buffalo , NY , USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Przespolewski
authors.affiliation: a Department of Medicine , Roswell Park Cancer Institute , Elm and Carlton Streets, Buffalo , NY , USA.
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D015195:Drug Design; D044127:Epigenesis, Genetic; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D056466:Histone Demethylases / Q000037:antagonists & inhibitors*; D006657:Histones / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Acute myeloid leukemia; LSD1; epigenetics; lysine specific demethylase; tranylcypromine analogues