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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3733-3739.
Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2005-06-2248.


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CLINICAL TRIALS AND OBSERVATIONS

Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype

Susanne Schnittger, Claudia Schoch, Wolfgang Kern, Cristina Mecucci, Claudia Tschulik, Massimo F. Martelli, Torsten Haferlach, Wolfgang Hiddemann, and Brunangelo Falini

From the Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilian's University, Munich, Germany; the Clinical Cooperative Group Acute Leukemia, Gesellschaft für Strahlenforschung (GSF) Research Center for Environment and Health, Munich, Germany; and the Institute of Hematology, Policlinico, Monteluce, Perugia, Italy.

Nucleophosmin (NPM1) exon-12 gene mutations are the hallmark of a large acute myelogenous leukemia (AML) subgroup with normal karyotype, but their prognostic value in this AML subset has not yet been determined. We screened 401 AML patients with normal karyotype treated within the German AML Cooperative Group Protocol 99 (AMLCG99) study for NPM1 mutations. Results were related with partial tandem duplications within the MLL gene (MLL-PTD), Fms-like tyrosine kinase 3–length mutations (FLT3-LM), the tyrosine kinase domain of FLT3 (FLT3-TKD), NRAS, KIT, and CEBPA mutations and with clinical characteristics and outcome. NPM1 mutations were detected in 212 (52.9%) of 401 patients. Fourteen mutations, including 8 new variants, were identified. NPM1-mutated cases associated frequently with FLT3 mutations but rarely with other mutations. The NPM1-mutated group had a higher complete remission (CR) rate (70.5% vs 54.7%, P = .003), a trend to a longer overall survival (OS; median 1012 vs 549 days, P = .076), and significantly longer event-free survival (EFS; median 428 vs 336 days; P = .012). The favorable impact of NPM1 mutations on OS and EFS clearly emerged in the large group (264 [66.8%] of 395 cases) of normal-karyotype AML without FLT3-LM. This positive effect was lost in the presence of a concomitant FLT3-LM, since survival of the NPM1+/FLT3-LM+ double positive was similar to NPM1/FLT3-LM+ cases. In conclusion, this study demonstrates that NPM1+/FLT3-LM mutations are an independent predictor for a favorable outcome in AML with normal karyotype.


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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.
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Cancer Res.Home page
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]


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ASH Education BookHome page
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]



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