Principal investigators

Prof. Dr. med. Konstanze Döhner
Department of Internal Medicine III
University of Ulm
Albert-Einstein-Allee 23
89081 Ulm
Phone: 0731-500-45501
konstanze.doehner(at)uniklinik-ulm.de

Curriculum Vitae

Prof. Dr. med. Lars Bullinger
Department of Internal Medicine III
University of Ulm
Albert-Einstein-Allee 23
89081 Ulm
Phone: 0731-500-45501
lars.bullinger(at)uniklinik-ulm.de

Curriculum Vitae

Summary

Acute myeloid leukemia (AML) with mutation of the nucleophosmin (NPM1) gene is characterized by distinct clinical and biological features. The goal of this project is to further unravel the molecular basis of this AML subtype by making use of integrative genomics approaches combining single-nucleotide-polymorphism (SNP) microarray analysis, gene expression profiling, and next-generation sequencing. This approach will allow us to detect secondary genetic events that subsequently will be further investigated at the functional level using in vitro and in vivo models. While these analyses will identify disease relevant genes and pathways involved in the pathogenesis of NPM1-mutated AML, findings will also be correlated with clinical data obtained from large treatment trials to reveal their potential prognostic and predictive impact.

B3

Molecular and functional characterization of cooperating events in acute myeloid leukemia with NPM1 mutation

Publications

Krönke J, Schlenk RF, Jensen KO, Tschürtz F, Corbacioglu A, Gaidzik VI, Paschka P, Onken S, Eiwen K, Habdank M, Späth D, Lübbert M, Wattad M, KindlerT, Salih HR, Held G, Nachbaur D, von Lilienfeld-Toal M, Germing U, Haase D, Mergenthaler HG, Krauter J, Ganser A, Göhring G, Schlegelberger B, Döhner H, Döhner K. Monitoring of Minimal Residual Disease in NPM1 Mutated Acute Myeloid Leukemia: A study of the German-Austrian AML Study Group (AMLSG). J Clin Oncol. 2011;29:2709-16.

Krönke J, Bullinger L, Rücker FG, Gaidzik VI, Kühn MWM, Bezet K, Teleanu V, Paschka P, Späth D, Kindler T, Salih HR, Krauter J, Ganser A, Göhring G, Schlegelberger B, Schlenk RF, Döhner H, Döhner K. Assessment of Clonal Evolution in 42 AML with NPM1 Mutations by Molecular Characterization of Paired Diagnosis and Relapse Samples Blood (ASH Annual Meeting Abstracts). 2011;118:237.

Paschka P, Schlenk RF, Herzig J, Aulitzky T, Gaidzik VI, Bullinger L, Habdank M, Corbacioglu A, Späth D, Köhne C, Kündgen A, von Lilienfeld-Toal M, Held G, Horst HA, Götze K, Bentz M, Krauter J, Ganser A, Döhner H, Döhner K. ASXL1 Μutations Predict for Resistance to Chemotherapy and Inferior Outcome in Younger Adult Patients with Acute Myeloid Leukemia (AML): A Study of the German-Austrian AMLSG. Blood (ASH Annual Meeting Abstracts). 2011;118:412

Taskesen E, Bullinger L, Corbacioglu A, Sanders M, Erpelinck C, Wouters BJ, van der Poel-van de Luytgaarde S, Damm F, Krauter J, Ganser A, Schlenk R, Löwenberg B, Delwel R, Döhner H, Valk P, Döhner K. Prognostic impact, concurrent genetic mutations and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011;117:2469-75.

Bullinger L, Ehrich M, Döhner K, Schlenk RF, Döhner H, Nelson MR, van den Boom D. Quantitative DNA-methylation predicts survival in adult acute myeloid leukemia. Blood. 2010;115(3):636-42.

Kohlmann A, Bullinger L, Thiede C, Schaich M, Schnittger S, Döhner K, Dugas M, Klein HU, Döhner H, Ehninger G, Haferlach T. Gene expression profiling in AML with normal karyotype can predict mutations for molecular markers and allows novel insights into perturbed biological pathways. Leukemia. 2010;24:1216-20.

Bullinger L, Krönke J, Schön C, Radtke I, Urlbauer K, Botzenhardt U, Gaidzik V, Carió A, Senger C, Schlenk RF, Downing JR, Holzmann K, Döhner K, Döhner H. Identification of Acquired Copy Number Alterations and Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia Using High-Resolution Single Nucleotide Polymorphism Analysis. Leukemia. 2010;24:438-49.

Paschka P, Schlenk RF, Gaidzik VI, Habdank M, Krönke J, Bullinger L, Späth D, Kayser S, Zucknick M, Götze K, Horst HA, Germing U, Döhner H, Döhner K. IDH1 and IDH2 Mutations are Frequent Genetic Alterations in Acute Myeloid Leukemia (AML) and Confer Adverse Prognosis in Cytogenetically Normal AML with NPM1 Mutation without FLT3-ITD. J Clin Oncol. 2010;28:3636-43.

Schlenk RF,* Dohner K,* Kneba M, Gotze K, Hartmann F, Del Valle F, Kirchen H, Koller E, Fischer JT, Bullinger L, Habdank M, Spath D, Groner S, Krebs B, Kayser S, Corbacioglu A, Anhalt A, Benner A, Frohling S, Dohner H. 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. 2009;94:54-60. *Equal contribution.

Schlenk RF,* Döhner K,* Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Döhner H, for the German-Austrian AML Study Group (AMLSG). Prognostic and predictive impact of gene mutations in younger adults with cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909-1918. *Equal contribution.

Corbacioglu A, Fröhling S, Paschka P, Marcucci G, Anhalt A, Urlbauer K, Krauter J, Larson RA, Mrózek K, Ruppert AS, Ganser, A, Caligiuri MA, Döhner H, Schlenk RF, Bloomfield CD, Döhner K. Acute Myeloid Leukemia (AML) with 9q Aberrations Occuring within a Non-Complex Karyotype Is Highly Associated with CEBPA and NPM1 Mutations - A Joint Analysis of the German-Austrian AML Study Group (AMLSG) and Cancer and Leukemia Group B (CALGB). Blood (ASH Annual Meeting Abstracts). 2007;110:762.

Döhner K, Schlenk RF, Habdank M, Scholl C, Rücker FG, Corbacioglu A, Bullinger L, Fröhling S, Döhner H. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics - interaction with other gene mutations. Blood. 2005;106:3740-3746.