title: Curing APL through PML/RARA degradation by As2O3.
abstract: Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the PML/RARA oncogene. The prognosis for patients with APL was revolutionized by two treatments: retinoic acid (RA) and As(2)O(3) (arsenic trioxide). These were both shown a posteriori to target PML/RARA, explaining their exquisite specificity for APL. Arsenic, as a single agent, cures up to 70% of patients, whereas APL patients treated with the combination of RA and As(2)O(3) reach a stunning 90% cure rate. Recent physiopathological models highlight the key role of RA- and As(2)O(3)-triggered PML/RARA degradation, and the molecular mechanisms underlying As(2)O(3)-induced PML/RARA degradation have been recently clarified. As discussed below, arsenic binding, oxidation, sumoylation on PML nuclear bodies, and RNF4-mediated ubiquitination all contribute to the As(2)O(3)-triggered catabolism of PML/RARA.
authors: University Paris Diderot, Sorbonne Paris Cité, Hôpital St Louis 1, Avenue Claude Vellefaux, 75475 Paris, Cedex 10, France.
authors: Valerie
authors: V
authors: Lallemand-Breitenbach
authors: Jun
authors: J
authors: Zhu
authors: Zhu
authors: Z
authors: Chen
authors: Hugues
authors: H
authors: de Thé
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058207:Sumoylation / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D000077237:Arsenic Trioxide