title: Epigenetics in acute promyelocytic leukaemia pathogenesis and treatment response: a TRAnsition to targeted therapies.
abstract: Transcriptional deregulation plays a key role in a large array of cancers, and successful targeting of oncogenic transcription factors that sustain diseases has been a holy grail in the field. Acute promyelocytic leukaemia (APL) driven by chimeric transcription factors encoding retinoic acid receptor alpha fusions is the paradigm of targeted cancer therapy, in which the application of all-trans retinoic acid (ATRA) treatments have markedly transformed this highly fatal cancer to a highly manageable disease. The extremely high complete remission rate resulted from targeted therapies using ATRA in combination with arsenic trioxide will likely be able to minimise or even totally eliminate the use of highly toxic chemotherapeutic agents in APL. In this article, we will review the molecular basis and the upcoming challenges of these targeted therapies in APL, and discuss the recent advance in our understanding of epigenetics underlying ATRA response and their potential use to further improve treatment response and overcome resistance.
authors.affiliation: Leukaemia and Stem Cell Biology Group, Department of Haematological Medicine, King's College London, Denmark Hill, London SE5 9NU, UK.
authors.forename: M F
authors.initials: MF
authors.lastname: Arteaga
authors.affiliation: Leukaemia and Stem Cell Biology Group, Department of Haematological Medicine, King's College London, Denmark Hill, London SE5 9NU, UK.
authors.forename: J-H
authors.initials: JH
authors.lastname: Mikesch
authors.affiliation: Leukaemia and Stem Cell Biology Group, Department of Haematological Medicine, King's College London, Denmark Hill, London SE5 9NU, UK.
authors.forename: T-K
authors.initials: TK
authors.lastname: Fung
authors.affiliation: Leukaemia and Stem Cell Biology Group, Department of Haematological Medicine, King's College London, Denmark Hill, London SE5 9NU, UK.
authors.forename: C W E
authors.initials: CW
authors.lastname: So
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods*; D010087:Oxides / Q000008:administration & dosage; D018168:Receptors, Retinoic Acid / Q000502:physiology; D000072482:Retinoic Acid Receptor alpha; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D001152:Arsenicals; D010087:Oxides; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D000077237:Arsenic Trioxide