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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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Submitted June 6, 2005
Accepted July 8, 2005

Nucleophosmin gene mutations are predictors of favourable prognosis in acute myelogenous leukemia with a normal kayotype

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

Department of Internal Medicine III, University Hospital Grosshadern, Ludwig Maximilians-University, Laboratory for Leukemia Diagnostics, Munich, Germany
Institute of Hematology, Policlinico, Perugia, Italy
Clinical Cooperative Group Acute Leukemia, GSF Research Centre for Environment and Health, Munich, Germany

* Corresponding author; email: susanne.schnittger{at}med.uni-muenchen.de.

Nucleophosmin (NPM) 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 AMLCG99 study for NPM mutations. Results were related with MLL-PTD, FLT3-LM, FLT3-TKD, NRAS, KIT, and CEBPA mutations and with clinical characteristics and outcome. NPM mutations were detected in 212/401 patients (52.9%). Fourteen mutations, including eight new variants, were identified. NPM-mutated cases associated frequently with FLT3 mutations but rarely with other mutations. The NPM-mutated group had a higher CR rate (70.5% vs. 54.7%, p=0.003), a trend to a longer OS (median 1012 vs. 549 days, p=0.0762), and significantly longer EFS (median 428 vs. 336 days; p=0.0121). The favourable impact of NPM mutations on OS and EFS clearly emerged in the large group (264/395 cases; 66.8%) of normal karyotype AML without FLT3-LM. This positive effect was lost in the presence of a concomitant FLT3-LM, since survival of the NPM+/FLT3-LM+ double positive was similar to NPM-/FLT3-LM+ cases. In conclusion, this study demonstrates that NPM+/FLT3-LM- mutations are an independent predictor for a favourable outcome in AML with normal karyotype.


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