Document Detail


Cytoplasmic localization of nucleophosmin in bone marrow blasts of acute myeloid leukemia patients is not completely concordant with NPM1 mutation and is not predictive of prognosis.
MedLine Citation:
PMID:  19637342     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Nucleophosmin (NPM1) gene mutations are reported to predict a favorable prognosis in acute myeloid leukemia (AML) patients. Aberrant cytoplasmic localization of nucleophosmin (NPM) protein is reported be a surrogate for NPM1 gene mutation.
METHODS: Using immunohistochemical (IHC) analysis, we assessed for NPM (clone 376) expression in formalin-fixed, formic acid-decalcified bone marrow biopsy specimens. DNA sequencing of exon 12 of NPM1 gene was performed in 104 patients.
RESULTS: The study included 252 AML patients: 192 de novo AML, 33 AML preceded by either myelodysplastic syndrome or chronic myelomonocytic leukemia, and 27 therapy-related AML. The median age was 62 years and 115 patients were <or=60 years old. All patients received intensive chemotherapy. Cytoplasmic NPM was detected in 59 of 252 (23%) patients, including 48 of 192 (25%) de novo AML and 33 of 94 (35%) with a normal karyotype. DNA sequencing identified NPM1 mutations in 30 of 38 cases with cytoplasmic NPM and 10 of 66 cases with nuclear NPM. Cytoplasmic NPM was associated with young patient age (P=.024), FLT3/ITD (P=.005), CD34 negative blasts (P<.001), high peripheral blood blast count (P=.041), and high serum albumin level (P=.028). No statistical differences in overall or event-free survival were found on the basis of NPM localization. Similar results were obtained in patients<or=60 years old with normal karyotype and wild-type FLT3 (P=.768).
CONCLUSIONS: IHC assessment for NPM localization did not predict prognosis in this patient cohort. The discordance between immunohistochemistry and DNA sequencing results indicates that DNA sequencing cannot be replaced by IHC assessment.
Authors:
Sergej Konoplev; Xuelin Huang; Harry A Drabkin; Hartmut Koeppen; Dan Jones; Hagop M Kantarjian; Guillermo Garcia-Manero; Weina Chen; L Jeffrey Medeiros; Carlos E Bueso-Ramos
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer     Volume:  115     ISSN:  0008-543X     ISO Abbreviation:  Cancer     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-13     Completed Date:  2009-12-01     Revised Date:  2014-10-18    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4737-44     Citation Subset:  AIM; IM    
Copyright Information:
Copyright (c) 2009 American Cancer Society.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Bone Marrow / metabolism*
Cytoplasm / metabolism*
Female
Humans
Immunohistochemistry
Leukemia, Myeloid, Acute / genetics*,  metabolism*
Male
Middle Aged
Mutation
Nuclear Proteins / genetics*,  metabolism*
Polymerase Chain Reaction
Prognosis
Survival Analysis
Grant Support
ID/Acronym/Agency:
P30 CA016672/CA/NCI NIH HHS; U54 CA096300/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 117896-08-9/nucleophosmin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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