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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4505-4511.
Prepublished online as a Blood First Edition Paper on February 12, 2009; DOI 10.1182/blood-2008-10-183392.


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Submitted October 15, 2008
Accepted February 2, 2009

Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia (AML): A study of the German-Austrian AML Study Group (AMLSG)

Verena Ingeborg Gaidzik, Richard Friedrich Schlenk, Simone Moschny, Annegret Becker, Lars Bullinger, Andrea Corbacioglu, Jurgen Krauter, Brigitte Schlegelberger, Arnold Ganser, Hartmut Dohner, and Konstanze Dohner*

Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplanation, Hannover Medical School, Hannover, Germany
Institute of Molecular and Cellular Pathology, Hannover Medical School, Hannover, Germany

* Corresponding author; email: konstanze.doehner{at}uniklinik-ulm.de.

To evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on three German-Austrian AML Study Group (AMLSG) protocols. WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54/78) and exon 9 (13/78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (p=0.0005) and CEBPA mutations (p=0.004). There was no difference in relapse-free survival (RFS), and overall survival (OS) between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission (CR) rate (p=0.003) and an inferior RFS (p=0.006) and OS (p<0.0001) compared to those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1mut/FLT3-ITDpos.


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D. Cilloni, A. Renneville, F. Hermitte, R. K. Hills, S. Daly, J. V. Jovanovic, E. Gottardi, M. Fava, S. Schnittger, T. Weiss, et al.
Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized WT1 Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study
J. Clin. Oncol., November 1, 2009; 27(31): 5195 - 5201.
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