title: Detection of nucleophosmin gene mutations in plasma from patients with acute myeloid leukemia: clinical significance and implications.
abstract: Roughly one-third of acute myeloid leukemia (AML) patients exhibit mutations in the nucleophosmin (NPM1) gene, and multiple studies have linked these mutations with a more favorable clinical outcome. We developed an assay for the detection of NPM1 mutations in peripheral blood plasma, and compared the results with clinical outcomes from a single institution. Analyzing plasma from previously untreated AML patients revealed NPM1 insertion mutations in 24 of 98 (24%) patients, with greater sensitivity than existing peripheral blood cell-based tests which showed positivity in only 22 of the 24 patients. Plasma testing allowed the detection of a novel 4 bp deletion in NPM1 in one patient. Analysis of clinical data corroborated previous data linking NPM1 mutations with better clinical outcome. These data underline the significance of NPM1 in the biology and clinical behavior of AML, and demonstrate the reliability and efficacy of plasma-based testing for NPM1 mutations.
authors.affiliation: Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, USA.
authors.forename: Wanlong
authors.initials: W
authors.lastname: Ma
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Iman
authors.initials: I
authors.lastname: Jilani
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Sheikholeslami
authors.forename: Amber C
authors.initials: AC
authors.lastname: Donahue
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Elihu
authors.initials: E
authors.lastname: Estey
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011379:Prognosis; D055815:Young Adult
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin