Journal
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Volume 133, Issue 1, Pages 34-40Publisher
OXFORD UNIV PRESS INC
DOI: 10.1309/AJCPCI1FFE2DRXIV
Keywords
Nucleophosmin, NPM1, Immunohistochemistry, Acute myeloid leukemia; Prognosis
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Funding
- Ontario Association of Medical Laboratories, Toronto
- Leukemia & Lymphoma Society of Canada, Toronto
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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 MPMc+ 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 I 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.
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