title: Cytoplasmic expression of nucleophosmin accurately predicts mutation in the nucleophosmin gene in patients with acute myeloid leukemia and normal karyotype.
abstract: Mutations in the nucleophosmin (NPM1) exon 12 resulting in delocalization of NPM1 into the cytoplasm occur in 50% to 60% of acute myeloid leukemia cases with a normal karyotype (AML-NK). As recent studies suggest such patients have a favorable prognosis and there are discordant reports of the immunohistochemical detection of cytoplasmic NPM1 (NPMc+) for predicting NPM1 gene mutations, we correlated the immunohistochemical detection of NPMc+, NPM1 gene mutations, and prognosis in 57 cases of AML-NK. All 31 NPMc+ cases (54% of total) had NPM1 mutations, but none of the 26 nucleus-restricted (NPMc-) cases (46% of total) had NPM1 mutations (P < .0001). NPM1 mutations were correlated with FLT3-internal tandem duplication (ITD) (P = .0062), absence of CD34 (P = .0001), and absence of CD7 (P = .041). There was a favorable survival outcome in AML-NK cases that were NPM1 mutated and FLT3-ITD nonmutated. Our data confirm that cytoplasmic NPM1 immunoreactivity predicts NPM1 mutations and warrants inclusion in the routine diagnostic and prognostic workup of AML.
authors.affiliation: Departments of 1Laboratory Hematology, University Health Network, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Luo
authors.forename: Connie
authors.initials: C
authors.lastname: Qi
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Joseph
authors.initials: J
authors.lastname: Brandwein
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D012074:Remission Induction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin