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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3747-3754. Prepublished online as a Blood First Edition Paper on August 18, 2005; DOI 10.1182/blood-2005-05-2168. This Article Full Text Full Text (PDF) Supplemental Table and Figure All Versions of this Article: 2005-05-2168v1 106/12/3747    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Verhaak, R. G. W. Articles by Valk, P. J. M. Search for Related Content PubMed PubMed Citation Articles by Verhaak, R. G. W. Articles by Valk, P. J. M. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance Roel G. W. Verhaak, Chantal S. Goudswaard, Wim van Putten, Maarten A. Bijl, Mathijs A. Sanders, Wendy Hugens, André G. Uitterlinden, Claudia A. J. Erpelinck, Ruud Delwel, Bob Löwenberg, and Peter J. M. Valk From the Departments of Hematology, Statistics, and Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. Mutations in nucleophosmin NPM1 are the most frequent acquired molecular abnormalities in acute myeloid leukemia (AML). We determined the NPM1 mutation status in a clinically and molecularly well-characterized patient cohort of 275 patients with newly diagnosed AML by denaturing high-performance liquid chromatography (dHPLC). We show that NPM1 mutations are significantly underrepresented in patients younger than 35 years. NPM1 mutations positively correlate with AML with high white blood cell counts, normal karyotypes, and fms-like tyrosine kinase-3 gene (FLT3) internal tandem duplication (ITD) mutations. NPM1 mutations associate inversely with the occurrence of CCAAT/enhancer-binding protein- (CEBPA) and NRAS mutations. With respect to gene expression profiling, we show that AML cases with an NPM1 mutation cluster in specific subtypes of AML with previously established gene expression signatures, are highly associated with a homeobox gene–specific expression signature, and can be predicted with high accuracy. We demonstrate that patients with intermediate cytogenetic risk AML without FLT3 ITD mutations but with NPM1 mutations have a significantly better overall survival (OS) and event-free survival (EFS) than those without NPM1 mutations. Finally, in multivariable analysis NPM1 mutations express independent favorable prognostic value with regard to OS, EFS, and disease-free survival (DFS). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dueling mutations in normal karyotype AML Robert E. Gallagher Blood 2005 106: 3681-3682. [Full Text] [PDF] This article has been cited by other articles: C. Langer, G. Marcucci, K. B. Holland, M. D. Radmacher, K. Maharry, P. Paschka, S. P. Whitman, K. Mrozek, C. D. Baldus, R. Vij, et al. Prognostic Importance of MN1 Transcript Levels, and Biologic Insights From MN1-Associated Gene and MicroRNA Expression Signatures in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., July 1, 2009; 27(19): 3198 - 3204. [Abstract] [Full Text] [PDF] 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. [Abstract] [Full Text] [PDF] U. Bacher, A. Kohlmann, and T. Haferlach Perspectives of gene expression profiling for diagnosis and therapy in haematological malignancies Brief Funct Genomic Proteomic, May 27, 2009; (2009) elp011v1. [Abstract] [Full Text] [PDF] F. Schneider, E. Hoster, M. Unterhalt, S. Schneider, A. Dufour, T. Benthaus, G. Mellert, E. Zellmeier, S. K. 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