Detection of nucleophosmin gene mutations in plasma from patients with acute myeloid leukemia: clinical significance and implications.
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.
Ma
Wanlong
W
Hematopathology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, USA.
Kantarjian
Hagop
H
Zhang
Xi
X
Jilani
Iman
I
Sheikholeslami
Mohammad R
MR
Donahue
Amber C
AC
Ravandi
Farhad
F
Estey
Elihu
E
O'Brien
Susan
S
Keating
Michael
M
Giles
Francis J
FJ
Albitar
Maher
M
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
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin