SEARCH:   Advanced

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. M. Santamaria, M. C. Chillon, R. Garcia-Sanz, C. Perez, M. D. Caballero, F. Ramos, A. G. de Coca, J. M. Alonso, P. Giraldo, T. Bernal, et al. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia Blood, July 2, 2009; 114(1): 148 - 152. [Abstract] [Full Text] [PDF] 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] J. Krauter, K. Wagner, I. Schafer, R. Marschalek, C. Meyer, G. Heil, M. Schaich, G. Ehninger, D. Niederwieser, R. Krahl, et al. Prognostic Factors in Adult Patients up to 60 Years Old With Acute Myeloid Leukemia and Translocations of Chromosome Band 11q23: Individual Patient Data-Based Meta-Analysis of the German Acute Myeloid Leukemia Intergroup J. Clin. Oncol., June 20, 2009; 27(18): 3000 - 3006. [Abstract] [Full Text] [PDF] F. Schneider, E. Hoster, M. Unterhalt, S. Schneider, A. Dufour, T. Benthaus, G. Mellert, E. Zellmeier, S. K. Bohlander, M. Feuring-Buske, et al. NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS) Blood, May 21, 2009; 113(21): 5250 - 5253. [Abstract] [Full Text] [PDF] B. C. Medeiros Role of CEBPA in Normal Karyotype Acute Myeloid Leukemia J. Clin. Oncol., April 20, 2009; 27(12): 2105 - 2105. [Full Text] [PDF] H. D. Klepin and L. Balducci Acute Myelogenous Leukemia in Older Adults Oncologist, March 1, 2009; 14(3): 222 - 232. [Abstract] [Full Text] [PDF] O. K. Weinberg, M. Seetharam, L. Ren, K. Seo, L. Ma, J. D. Merker, J. Gotlib, J. L. Zehnder, and D. A. Arber Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system Blood, February 26, 2009; 113(9): 1906 - 1908. [Abstract] [Full Text] [PDF] S. Koschmieder, B. Halmos, E. Levantini, and D. G. Tenen Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer J. Clin. Oncol., February 1, 2009; 27(4): 619 - 628. [Abstract] [Full Text] [PDF] B. C. Medeiros Comparing Apples and Oranges in Normal Karyotype Acute Myeloid Leukemia J. Clin. Oncol., January 20, 2009; 27(3): 474 - 474. [Full Text] [PDF] T. Buchner, W. E. Berdel, C. Haferlach, T. Haferlach, S. Schnittger, C. Muller-Tidow, J. Braess, K. Spiekermann, J. Kienast, P. Staib, et al. Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group J. Clin. Oncol., January 1, 2009; 27(1): 61 - 69. [Abstract] [Full Text] [PDF] R. F. Schlenk, K. Dohner, M. Kneba, K. Gotze, F. Hartmann, F. del Valle, H. Kirchen, E. Koller, J. T. Fischer, L. Bullinger, et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B Haematologica, January 1, 2009; 94(1): 54 - 60. [Abstract] [Full Text] [PDF] R. G.W. Verhaak, B. J. Wouters, C. A.J. Erpelinck, S. Abbas, H. B. Beverloo, S. Lugthart, B. Lowenberg, R. Delwel, and P. J.M. Valk Prediction of molecular subtypes in acute myeloid leukemia based on gene expression profiling Haematologica, January 1, 2009; 94(1): 131 - 134. [Abstract] [Full Text] [PDF] 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. 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] C. Langer, M. D. Radmacher, A. S. Ruppert, S. P. Whitman, P. Paschka, K. Mrozek, C. D. Baldus, T. Vukosavljevic, C.-G. Liu, M. E. Ross, et al. High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study Blood, June 1, 2008; 111(11): 5371 - 5379. [Abstract] [Full Text] [PDF] M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. Lowenberg MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia Blood, May 15, 2008; 111(10): 5078 - 5085. [Abstract] [Full Text] [PDF] R. F. Schlenk, K. Dohner, J. Krauter, S. Frohling, A. Corbacioglu, L. Bullinger, M. Habdank, D. Spath, M. Morgan, A. Benner, et al. Mutations and Treatment Outcome in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1909 - 1918. [Abstract] [Full Text] [PDF] G. Marcucci, M. D. Radmacher, K. Maharry, K. Mrozek, A. S. Ruppert, P. Paschka, T. Vukosavljevic, S. P. Whitman, C. D. Baldus, C. Langer, et al. MicroRNA Expression in Cytogenetically Normal Acute Myeloid Leukemia N. Engl. J. Med., May 1, 2008; 358(18): 1919 - 1928. [Abstract] [Full Text] [PDF] T. Ottone, E. Ammatuna, S. Lavorgna, N. I. Noguera, F. Buccisano, A. Venditti, L. Gianni, M. Postorino, G. Federici, S. Amadori, et al. An Allele-Specific RT-PCR Assay to Detect Type A Mutation of the Nucleophosmin-1 Gene in Acute Myeloid Leukemia J. Mol. Diagn., May 1, 2008; 10(3): 212 - 216. [Abstract] [Full Text] [PDF] G. Wertheim and A. Bagg Nucleophosmin (NPM1) Mutations in Acute Myeloid Leukemia: An Ongoing (Cytoplasmic) Tale of Dueling Mutations and Duality of Molecular Genetic Testing Methodologies J. Mol. Diagn., May 1, 2008; 10(3): 198 - 202. [Abstract] [Full Text] [PDF] P. Szankasi, M. Jama, and D. W. Bahler A New DNA-Based Test for Detection of Nucleophosmin Exon 12 Mutations by Capillary Electrophoresis J. Mol. Diagn., May 1, 2008; 10(3): 236 - 241. [Abstract] [Full Text] [PDF] L. Bullinger, K. Dohner, R. Kranz, C. Stirner, S. Frohling, C. Scholl, Y. H. Kim, R. F. Schlenk, R. Tibshirani, H. Dohner, et al. An FLT3 gene-expression signature predicts clinical outcome in normal karyotype AML Blood, May 1, 2008; 111(9): 4490 - 4495. [Abstract] [Full Text] [PDF] R. E. Gale, C. Green, C. Allen, A. J. Mead, A. K. Burnett, R. K. Hills, D. C. Linch, and on behalf of the Medical Research Council Adult Le The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia Blood, March 1, 2008; 111(5): 2776 - 2784. [Abstract] [Full Text] [PDF] S. P. Whitman, A. S. Ruppert, M. D. Radmacher, K. Mrozek, P. Paschka, C. Langer, C. D. Baldus, J. Wen, F. Racke, B. L. Powell, et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications Blood, February 1, 2008; 111(3): 1552 - 1559. [Abstract] [Full Text] [PDF] R. M. Stone Genetically Defined Prognostic Factors and Novel Therapeutics for AML ASCO Educational Book, January 1, 2008; 2008(1): 280 - 284. [Abstract] [Full Text] [PDF] W. Zhang, J.-M. Navenot, N. M. Frilot, N. Fujii, and S. C. Peiper Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis Mol. Pharmacol., November 1, 2007; 72(5): 1310 - 1321. [Abstract] [Full Text] [PDF] L. Bullinger, F. G. Rucker, S. Kurz, J. Du, C. Scholl, S. Sander, A. Corbacioglu, C. Lottaz, J. Krauter, S. Frohling, et al. Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia Blood, August 15, 2007; 110(4): 1291 - 1300. [Abstract] [Full Text] [PDF] G. Marcucci, K. Maharry, S. P. Whitman, T. Vukosavljevic, P. Paschka, C. Langer, K. Mrozek, C. D. Baldus, A. J. Carroll, B. L. Powell, et al. High Expression Levels of the ETS-Related Gene, ERG, Predict Adverse Outcome and Improve Molecular Risk-Based Classification of Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study J. Clin. Oncol., August 1, 2007; 25(22): 3337 - 3343. [Abstract] [Full Text] [PDF] P. Brown, E. McIntyre, R. Rau, S. Meshinchi, N. Lacayo, G. Dahl, T. A. Alonzo, M. Chang, R. J. Arceci, and D. Small The incidence and clinical significance of nucleophosmin mutations in childhood AML Blood, August 1, 2007; 110(3): 979 - 985. [Abstract] [Full Text] [PDF] N. Bolli, I. Nicoletti, M. F. De Marco, B. Bigerna, A. Pucciarini, R. Mannucci, M. P. Martelli, A. Liso, C. Mecucci, F. Fabbiano, et al. Born to Be Exported: COOH-Terminal Nuclear Export Signals of Different Strength Ensure Cytoplasmic Accumulation of Nucleophosmin Leukemic Mutants Cancer Res., July 1, 2007; 67(13): 6230 - 6237. [Abstract] [Full Text] [PDF] S. P. Whitman, A. S. Ruppert, G. Marcucci, K. Mrozek, P. Paschka, C. Langer, C. D. Baldus, J. Wen, T. Vukosavljevic, B. L. Powell, et al. Long-term disease-free survivors with cytogenetically normal acute myeloid leukemia and MLL partial tandem duplication: a Cancer and Leukemia Group B study Blood, June 15, 2007; 109(12): 5164 - 5167. [Abstract] [Full Text] [PDF] B. Falini, I. Nicoletti, N. Bolli, M. P. Martelli, A. Liso, P. Gorello, F. Mandelli, C. Mecucci, and M. F. Martelli Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias Haematologica, April 1, 2007; 92(4): 519 - 532. [Abstract] [Full Text] [PDF] B. Falini, I. Nicoletti, M. F. Martelli, and C. Mecucci Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features Blood, February 1, 2007; 109(3): 874 - 885. [Abstract] [Full Text] [PDF] K. Mrozek, G. Marcucci, P. Paschka, S. P. Whitman, and C. D. Bloomfield Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood, January 15, 2007; 109(2): 431 - 448. [Abstract] [Full Text] [PDF] J. Pedersen-Bjergaard, M. T. Andersen, and M. K. Andersen Genetic Pathways in the Pathogenesis of Therapy-Related Myelodysplasia and Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 392 - 397. [Abstract] [Full Text] [PDF] H. Dohner Implication of the Molecular Characterization of Acute Myeloid Leukemia Hematology, January 1, 2007; 2007(1): 412 - 419. [Abstract] [Full Text] [PDF] A. K. Burnett and S. Knapper Targeting Treatment in AML Hematology, January 1, 2007; 2007(1): 429 - 434. [Abstract] [Full Text] [PDF] L. Pasqualucci, A. Liso, M. P. Martelli, N. Bolli, R. Pacini, A. Tabarrini, M. Carini, B. Bigerna, A. Pucciarini, R. Mannucci, et al. Mutated nucleophosmin detects clonal multilineage involvement in acute myeloid leukemia: impact on WHO classification Blood, December 15, 2006; 108(13): 4146 - 4155. [Abstract] [Full Text] [PDF] M. Heuser, G. Beutel, J. Krauter, K. Dohner, N. von Neuhoff, B. Schlegelberger, and A. Ganser High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics Blood, December 1, 2006; 108(12): 3898 - 3905. [Abstract] [Full Text] [PDF] S. Frohling, R. F. Schlenk, S. Kayser, M. Morhardt, A. Benner, K. Dohner, H. Dohner, and for the German-Austrian AML Study Group Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B Blood, November 15, 2006; 108(10): 3280 - 3288. [Abstract] [Full Text] [PDF] B. Falini, M. P. Martelli, N. Bolli, R. Bonasso, E. Ghia, M. T. Pallotta, D. Diverio, I. Nicoletti, R. Pacini, A. Tabarrini, et al. Immunohistochemistry predicts nucleophosmin (NPM) mutations in acute myeloid leukemia Blood, September 15, 2006; 108(6): 1999 - 2005. [Abstract] [Full Text] [PDF] W. Chen, G. Z. Rassidakis, J. Li, M. Routbort, D. Jones, H. Kantarjian, L. J. Medeiros, and C. E. Bueso-Ramos High frequency of NPM1 gene mutations in acute myeloid leukemia with prominent nuclear invaginations ("cuplike" nuclei). Blood, September 1, 2006; 108(5): 1783 - 1784. [Full Text] [PDF] M. D. Radmacher, G. Marcucci, A. S. Ruppert, K. Mrozek, S. P. Whitman, J. W. Vardiman, P. Paschka, T. Vukosavljevic, C. D. Baldus, J. E. Kolitz, et al. Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study Blood, September 1, 2006; 108(5): 1677 - 1683. [Abstract] [Full Text] [PDF] C. S. Wilson, G. S. Davidson, S. B. Martin, E. Andries, J. Potter, R. Harvey, K. Ar, Y. Xu, K. J. Kopecky, D. P. Ankerst, et al. Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction Blood, July 15, 2006; 108(2): 685 - 696. [Abstract] [Full Text] [PDF] S. S. Farag, K. J. Archer, K. Mrozek, A. S. Ruppert, A. J. Carroll, J. W. Vardiman, M. J. Pettenati, M. R. Baer, M. B. Qumsiyeh, P. R. Koduru, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461 Blood, July 1, 2006; 108(1): 63 - 73. [Abstract] [Full Text] [PDF] B. Falini, N. Bolli, J. Shan, M. P. Martelli, A. Liso, A. Pucciarini, B. Bigerna, L. Pasqualucci, R. Mannucci, R. Rosati, et al. Both carboxy-terminus NES motif and mutated tryptophan(s) are crucial for aberrant nuclear export of nucleophosmin leukemic mutants in NPMc+ AML Blood, June 1, 2006; 107(11): 4514 - 4523. [Abstract] [Full Text] [PDF] C. Thiede, S. Koch, E. Creutzig, C. Steudel, T. Illmer, M. Schaich, G. Ehninger, and for the Deutsche Studieninitiative Leukamie (DSIL) Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML) Blood, May 15, 2006; 107(10): 4011 - 4020. [Abstract] [Full Text] [PDF] G. Roti, R. Rosati, R. Bonasso, P. Gorello, D. Diverio, M. F. Martelli, B. Falini, C. Mecucci, and for the Gruppo Italiano Malattie Ematologiche dell Denaturing High-Performance Liquid Chromatography: A Valid Approach for Identifying NPM1 Mutations in Acute Myeloid Leukemia J. Mol. Diagn., May 1, 2006; 8(2): 254 - 259. [Abstract] [Full Text] [PDF] W.-C. Chou, J.-L. Tang, L.-I. Lin, M. Yao, W. Tsay, C.-Y. Chen, S.-J. Wu, C.-F. Huang, R.-J. Chiou, M.-H. Tseng, et al. Nucleophosmin Mutations in De novo Acute Myeloid Leukemia: The Age-Dependent Incidences and the Stability during Disease Evolution. Cancer Res., March 15, 2006; 66(6): 3310 - 3316. [Abstract] [Full Text] [PDF] K. Mrozek and C. D. Bloomfield Chromosome Aberrations, Gene Mutations and Expression Changes, and Prognosis in Adult Acute Myeloid Leukemia Hematology, January 1, 2006; 2006(1): 169 - 177. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020