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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4011-4020. Prepublished online as a Blood First Edition Paper on February 2, 2006; DOI 10.1182/blood-2005-08-3167. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3167v1 107/10/4011    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 Thiede, C. Articles by Ehninger, G. Search for Related Content PubMed PubMed Citation Articles by Thiede, C. Articles by Ehninger, G. Related Collections Oncogenes and Tumor Suppressors Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML) Christian Thiede, Sina Koch, Eva Creutzig, Christine Steudel, Thomas Illmer, Markus Schaich, Gerhard Ehninger, for the Deutsche Studieninitiative Leukämie (DSIL) From the Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der Technischen Universität, Dresden, Germany. Mutations of the nucleophosmin (NPM1) gene have recently been described in patients with acute myeloid leukemia (AML). To clarify the prevalence as well as the clinical impact of this mutation, we investigated 1485 patients with AML for NPM1 exon 12 mutations using fragment analysis. A 4 bp insert was detected in 408 of 1485 patients (27.5%). Sequence analysis revealed known mutations (type A, B, and D) as well as 13 novel alterations in 229 analyzed cases. NPM1 mutations were most prevalent in patients with normal karyotype (NK) (324 of 709; 45.7%) compared with 58 of 686 with karyotype abnormalities (8.5%; P < .001) and were significantly associated with several clinical parameters (high bone marrow [BM] blasts, high white blood cell [WBC] and platelet counts, female sex). NPM1 alterations were associated with FLT3-ITD mutations, even if restricted to patients with NK (NPM1-mut/FLT3-ITD: 43.8%; versus NPM1-wt/FLT3-ITD: 19.9%; P < .001). The analysis of the clinical impact in 4 groups (NPM1 and FLT3-ITD single mutants, double mutants, and wild-type [wt] for both) revealed that patients having only an NPM1 mutation had a significantly better overall and disease-free survival and a lower cumulative incidence of relapse. In conclusion, NPM1 mutations represent a common genetic abnormality in adult AML. If not associated with FLT3-ITD mutations, mutant NPM1 appears to identify patients with improved response toward treatment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. S. Laughlin, M. W. Becker, J. L. Liesveld, D. A. Mulford, C. N. Abboud, P. Brown, and P. G. Rothberg Rapid Method for Detection of Mutations in the Nucleophosmin Gene in Acute Myeloid Leukemia J. Mol. Diagn., July 1, 2008; 10(4): 338 - 345. [Abstract] [Full Text] [PDF] F. Lo-Coco, A. Cuneo, F. Pane, D. Cilloni, D. Diverio, M. Mancini, N. Testoni, A. Bardi, B. Izzo, N. Bolli, et al. Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia Haematologica, July 1, 2008; 93(7): 1017 - 1024. [Abstract] [Full Text] [PDF] M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. 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