title: PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy.
abstract: The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cicconi
authors.affiliation: Laboratorio di Oncoematologia, Policlinico Tor Vergata, Roma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Divona
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ciardi
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Ottone
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ferrantini
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Lavorgna
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Alfonso
authors.affiliation: Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Data Center, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Paoloni
authors.affiliation: Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Data Center, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Piciocchi
authors.affiliation: Dipartimento di Ematologia, Università Campus Biomedico, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Avvisati
authors.affiliation: Dipartimento di Ematologia e Trapianto di Cellule Staminali, Ospedale Cardarelli, Napoli, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ferrara
authors.affiliation: Dipartimento di Terapie cellulari ed Ematologia, Unità Operativa di Ematologia, Vicenza, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Di Bona
authors.affiliation: Dipartimento di Ematologia, Università di Bari, Bari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Albano
authors.affiliation: Dipartimento di Biotecnologie Cellulari ed Ematologia, Università La Sapienza, Roma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Breccia
authors.affiliation: Dipartimento di Ematologia, Spedali Civili, Brescia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cerqui
authors.affiliation: Dipartimento di Ematologia, Ospedale Civile, Pescara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Sborgia
authors.affiliation: Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Kropp
authors.affiliation: Divisione di Ematologia e Unità di Trapianti di Midollo Osseo, Ospedale Riuniti Villa Sofia-Cervello, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Dipartimento di Oncoematologia, Sopedale SS Antonio e Biagio, Alessandria, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Levis
authors.affiliation: Università Cattolica Sacro Cuore, Roma.
authors.forename: S
authors.initials: S
authors.lastname: Sica
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Amadori
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Voso
authors.affiliation: Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Data Center, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mandelli
authors.affiliation: Dipartimento di Biomedicina e Prevenzione, Università degli studi Tor Vergata, Roma, Italy.|Santa Lucia Foundation, Roma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Lo-Coco
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007558:Italy; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000097:blood*; D010087:Oxides / Q000008:administration & dosage* / Q000627:therapeutic use; D011379:Prognosis; D014212:Tretinoin / Q000008:administration & dosage* / Q000627:therapeutic use; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D001152:Arsenicals; D015514:Oncogene Proteins, Fusion; D010087:Oxides; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D051941:fms-Like Tyrosine Kinase 3; D000077237:Arsenic Trioxide