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Blood, 1 August 2007, Vol. 110, No. 3, pp. 979-985. Prepublished online as a Blood First Edition Paper on April 17, 2007; DOI 10.1182/blood-2007-02-076604. This Article Full Text (PDF) All Versions of this Article: blood-2007-02-076604v1 110/3/979    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Brown, P. Articles by Small, D. Search for Related Content PubMed PubMed Citation Articles by Brown, P. Articles by Small, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 26, 2007 Accepted April 15, 2007 The incidence and clinical significance of nucleophosmin mutations in childhood AML Patrick Brown*, Emily McIntyre, Rachel Rau, Soheil Meshinchi, Norman Lacayo, Gary Dahl, Todd A Alonzo, Myron Chang, Robert J Arceci, and Donald Small Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States Department of Pediatrics, University of Washington Medical Center, Seattle, WA, United States Division of Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, CA, United States Children's Oncology Group, Arcadia, CA, United States Biostatistics, Children's Oncology Group Statistical Office, Gainesville, FL, United States Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States * Corresponding author; email: pbrown2{at}jhmi.edu. Frameshift mutations in exon 12 of the nucleophosmin gene (NPM1) result in aberrant cytoplasmic localization of the NPM protein (NPMc+) and occur in 25-35% of adult AML. In adults with AML, NPMc+ has been associated with normal karyotype, FLT3/ITD mutations, high remission induction rates and improved survival (particularly in patients lacking FLT3/ITD). NPMc+ has not been well-characterized in childhood AML. This study examines the incidence and clinical significance of NPMc+ in 295 children with newly diagnosed AML treated on a large cooperative group clinical trial (POG-9421). We find that NPMc+ is relatively uncommon in childhood AML (23 of 295 patients, 8%); and is significantly associated with FLT3/ITD mutations (p=0.046), female gender (p=0.029), older age (p=0.047) and normal cytogenetics (p<0.0001). There is a favorable impact of NPMc+ on survival in children lacking FLT3/ITD (5 year EFS 69% vs. 35%, hazard ratio 0.39, p=0.051), which is similar in magnitude to the favorable impact of t(8;21) and inv(16). We conclude that NPMc+ is relatively rare in childhood AML, particularly in younger children. NPMc+ does not abrogate the negative prognostic influence of FLT3/ITD mutations, but may contribute to risk stratification in children who lack FLT3/ITD mutations by identifying a group with superior prognosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. A. Ho, T. A. Alonzo, R. B. Gerbing, J. Pollard, D. L. Stirewalt, C. Hurwitz, N. A. Heerema, B. Hirsch, S. C. Raimondi, B. Lange, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group Blood, June 25, 2009; 113(26): 6558 - 6566. 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