Cytoplasmic expression of nucleophosmin accurately predicts mutation in the nucleophosmin gene in patients with acute myeloid leukemia and normal karyotype.
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.
Luo
Jennifer
J
Departments of 1Laboratory Hematology, University Health Network, and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Qi
Connie
C
Xu
Wei
W
Kamel-Reid
Suzanne
S
Brandwein
Joseph
J
Chang
Hong
H
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
D004273:DNA, Neoplasm; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin