title: Prognostic significance of FLT3 internal tandem duplication and NPM1 mutations in acute myeloid leukemia in an unselected patient population.
abstract: Mutations in the fms-like tyrosine kinase 3 (FLT3) gene containing an internal tandem duplication (FLT3/ITD) or mutations in the nucleophosmin 1 gene (NPM1) are thought to be prognostic indicators in acute myeloid leukemia (AML). Previous studies suggested that FLT3/ITD mutation indicates a poor prognosis and that NPM1 mutation indicates a more favorable one, but these studies were often performed with selected patient populations. We investigated the clinical significance of these mutations at our institution with an unselected group of patients with newly diagnosed AML. This group included patients > or =60 years old and those with a poor performance status. Using polymerase chain reaction and sequencing analyses, we detected FLT3/ITD mutations in 12 patients (20.0%) and NPM1 mutations in 7 patients (11.7%) among a group of 60 patients. There was a nonsignificant trend for FLT3/ITD mutation to be associated with a poorer predicted overall survival (OS) probability in this population. In contrast, OS was significantly higher in patients with wild-type NPM1 than in patients with NPM1 mutation, both for all AML patients and for AML patients with a normal karyotype. In this general and unselected AML patient population, NPM1 mutation was not a prognostic indicator of a favorable outcome.
authors.affiliation: Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Rikio
authors.initials: R
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Onizuka
authors.forename: Minoru
authors.initials: M
authors.lastname: Kojima
authors.forename: Masako
authors.initials: M
authors.lastname: Shimada
authors.forename: Kaori
authors.initials: K
authors.lastname: Okamura
authors.forename: Satomi
authors.initials: S
authors.lastname: Fukagawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Ako
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Shintani
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawada
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D015996:Survival Rate; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3