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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3740-3746. Prepublished online as a Blood First Edition Paper on July 28, 2005; DOI 10.1182/blood-2005-05-2164. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-2164v1 106/12/3740    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 Döhner, K. Articles by Döhner, H. Search for Related Content PubMed PubMed Citation Articles by Döhner, K. Articles by Döhner, H. Related Collections Neoplasia 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 Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations Konstanze Döhner, Richard F. Schlenk, Marianne Habdank, Claudia Scholl, Frank G. Rücker, Andrea Corbacioglu, Lars Bullinger, Stefan Fröhling, Hartmut Döhner, for the AML Study Group (AMLSG) From the Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany; and the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. To assess the prognostic relevance of mutations in the NPM1 gene encoding a nucleocytoplasmic shuttle protein in younger adults with acute myeloid leukemia (AML) and normal cytogenetics, sequencing of NPM1 exon 12 was performed in diagnostic samples from 300 patients entered into 2 consecutive multicenter trials of the AML Study Group (AMLSG). Treatment included intensive double-induction therapy and consolidation therapy with high cumulative doses of high-dose cytarabine. NPM1 mutations were identified in 48% of the patients including 12 novel sequence variants, all leading to a frameshift in the C-terminus of the nucleophosmin 1 (NPM1) protein. Mutant NPM1 was associated with specific clinical, phenotypical, and genetic features. Statistical analysis revealed a significant interaction of NPM1 and FLT3 internal tandem duplications (ITDs). NPM1 mutations predicted for better response to induction therapy and for favorable overall survival (OS) only in the absence of FLT3 ITD. Multivariable analysis for OS revealed combined NPM1-mutated/FLT3 ITD–negative status, CEBPA mutation status, availability of a human leukocyte antigen (HLA)–compatible donor, secondary AML, and lactate dehydrogenase (LDH) as prognostic factors. In conclusion, NPM1 mutations in the absence of FLT3 ITD define a distinct molecular and prognostic subclass of young-adult AML patients with normal cytogenetics. 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. Boonthimat, W. Thongnoppakhun, and C. U. Auewarakul Nucleophosmin mutation in Southeast Asian acute myeloid leukemia: eight novel variants, FLT3 coexistence and prognostic impact of NPM1/FLT3 mutations Haematologica, October 1, 2008; 93(10): 1565 - 1569. [Abstract] [Full Text] [PDF] T. S. Laughlin, M. W. 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