title: Molecular analysis and clinical outcome of adult APL patients with the type V PML-RARalpha isoform: results from intergroup protocol 0129.
abstract: The type V (for variable) promyelocytic leukemia retinoic acid receptor (PML-RAR)alpha transcript, found in approximately 8% of adult patients with acute promyelocytic leukemia (APL), is defined molecularly by truncation of PML exon 6 and frequent insertion of genetic material from RARalpha intron 2. To more fully characterize the molecular features of PML-RARalpha V-type transcripts and to determine whether V-form APL patients have a distinct clinical presentation or prognosis, we analyzed 18 adult V-form APL patients enrolled on Intergroup protocol 0129 (INT-0129). Truncations in PML exon 6 ranged from 8 to 146 nucleotides, and 3 to 127 extra nucleotides (1 to 42 extra amino acids) were inserted at the PML exon 6/RARalpha exon 3 junction in 13 cases. No distinguishing morphologic, cytogenetic, or immunophenotypic features of V-form blasts were identified. A total of 5 of 7 patients induced with ATRA and 8 of 11 patients who received chemotherapy for induction achieved complete remission (CR). Six patients have relapsed, 4 after chemotherapy induction and 2 after ATRA. Nine patients (50%) are alive, 6 in continuous CR, 2 after salvage therapy for relapsed or refractory disease, and 1 after alternative treatment following early removal from protocol. Although the failure rate for V-form APL patients was high (61%), the low power of the current study to detect clinically significant differences precludes a meaningful comparison of clinical outcomes between the 18 V-form cases and non-V-form adult APL patients enrolled on INT-0129. (Blood. 2000;95:398-403)
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. james.slack@roswellpark.org
authors.forename: J L
authors.initials: JL
authors.lastname: Slack
authors.forename: C L
authors.initials: CL
authors.lastname: Willman
authors.forename: J W
authors.initials: JW
authors.lastname: Andersen
authors.forename: Y P
authors.initials: YP
authors.lastname: Li
authors.forename: D S
authors.initials: DS
authors.lastname: Viswanatha
authors.forename: C D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: M S
authors.initials: MS
authors.lastname: Tallman
authors.forename: R E
authors.initials: RE
authors.lastname: Gallagher
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005091:Exons; D005260:Female; D006801:Humans; D007621:Karyotyping; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics; D012074:Remission Induction; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D003561:Cytarabine; D014212:Tretinoin; D003630:Daunorubicin