title: Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia.
abstract: Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance.
authors.affiliation: Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.|Laboratory of Neuro-Oncohematology, Fondazione Santa Lucia I.R.C.C.S, Rome, Italy.
authors.forename: Licia
authors.initials: L
authors.lastname: Iaccarino
authors.affiliation: Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.|Laboratory of Neuro-Oncohematology, Fondazione Santa Lucia I.R.C.C.S, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Ottone
authors.affiliation: Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.
authors.forename: Mariadomenica
authors.initials: M
authors.lastname: Divona
authors.affiliation: Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Cicconi
authors.affiliation: Division of Haematology, Niguarda Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cairoli
authors.affiliation: Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Voso
authors.affiliation: Department of Biomedicine and Prevention, Università di Roma "Tor Vergata", Rome, Italy.|Laboratory of Neuro-Oncohematology, Fondazione Santa Lucia I.R.C.C.S, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lo-Coco
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010087:Oxides / Q000627:therapeutic use; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010087:Oxides; D000071156:Promyelocytic Leukemia Protein; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D000077237:Arsenic Trioxide
keywords: ATO resistance; ATRA; PML and RARA mutations; acute promyelocytic leukaemia; clonal selection