title: Isoforms of PML-retinoic acid receptor alpha fused transcripts affect neither clinical features of acute promyelocytic leukemia nor prognosis after treatment with all-trans retinoic acid. The Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).
abstract: All-trans retinoic acid (ATRA) has been used as a potent differentiation drug for acute promyelocytic leukemia (APL). Although the mechanism of its effectiveness upon APL remains unclear, the PML-retinoic acid receptor alpha (RARA) chimeric protein produced by t(15;17) is assumed to underlie the sensitivity of APL cells to ATRA. There are two major isoforms of PML-RARA transcripts; short (S) and long (L), according to the breakpoints in the PML gene. We therefore compared the clinical variables, the response to ATRA and the prognosis between 28 patients with type S and 68 patients with type L. Patients were treated in multi-institutional trials with ATRA, and chemotherapy was combined when peripheral blasts and leukocyte counts increased during the therapy. The clinical features at diagnosis were similar between the two molecular subtypes, and there was no significant difference in remission induction rates; 86% for the type S group and 90% for the type L group. There was no statistical difference in overall survival and CR duration as well as disease-free survival (DFS). In newly diagnosed patients, predicted 2-year DFS was 66% for the type S group and 67% for the type L group. In refractory or relapsed patients, it was 19 and 23%, respectively. These data indicated that isoforms of PML-RARA fused transcripts affect neither the clinical features of APL nor the prognosis after treatment with ATRA.
authors.affiliation: Department of Internal Medicine, Nagoya University Branch Hospital, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukutani
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Miyawaki
authors.forename: C
authors.initials: C
authors.lastname: Shimazaki
authors.forename: T
authors.initials: T
authors.lastname: Miyake
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Goto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000502:physiology*; D011379:Prognosis; D016019:Survival Analysis; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin