Principal investigators

Prof. Dr. med. Stephan Stilgenbauer
Department of Internal Medicine III
University of Ulm
Albert-Einstein-Allee 23
89081 Ulm
Phone: 0731-500-45521
stephan.stilgenbauer(at)uniklinik-ulm.de

Curriculum vitae

PD Dr. rer. nat. Daniel Mertens                                              
Department of Internal Medicine III
University of Ulm
Albert-Einstein-Allee 23
89081 Ulm
Phone: 0731/500-45870
daniel.mertens(at)uniklinik-ulm.de

Curriculum vitae

Prof. Dr. med. Hartmut Döhner
Department of Internal Medicine III
University of Ulm
Albert-Einstein-Allee 23
89081 Ulm
Phone: 0731-500-45501 / +49-731-500-45505
hartmut.doehner(at)uniklinik-ulm.de

Curriculum Vitae


 

Summary

Genomic and epigenetic aberrations play an important role in CLL. Using genome-wide approaches we have identified novel genomic lesions. These findings will be complemented by targeted mutation and whole epigenome and transcriptome analyses. The comprehensive data sets will be subjected to integrative analysis including clinical characteristics and yield a set of candidate genes. Deregulated pathways will be investigated by functional analyses using viral transduction of leukemia cells and use of reporter assays. Patterns of target gene deregulations will allow identification of compounds that induce a complementary gene expression pattern. This strategy will characterize (epi)genetic lesions specific to CLL and will identify novel candidate compounds of potential therapeutic usefulness.

Publications

TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial.
Schnaiter A, Paschka P, Rossi M, Zenz T, Bühler A, Winkler D, Cazzola M, Döhner K, Edelmann J, Mertens D, Kless S, Mack S, Busch R, Hallek M, Döhner H, Stilgenbauer S. Blood. 2013, July 02. [Epub ahead of print]

TP53, SF3B1, and NOTCH1 mutations and outcome of allotransplantation for chronic lymphocytic leukemia: six-year follow-up of the GCLLSG CLL3X trial.
Dreger P, Schnaiter A, Zenz T, Böttcher S, Rossi M, Paschka P, Bühler A, Dietrich S, Busch R, Ritgen M, Bunjes D, Zeis M, Stadler M, Uharek L, Scheid C, Hegenbart U, Hallek M, Kneba M, Schmitz N, Döhner H, Stilgenbauer S.  Blood. 2013 Feb 22. [Epub ahead of print]

Sequencing of the childhood brain tumor medulloblastoma links catastrophic DNA rearrangements with TP53 mutations.
Rausch T, Jones DTW, Zapatka M, Stütz AM, Zichner T, Weischenfeldt J, Jäger N, Remke M, Shih D, Northcott PA, Pfaff E, Tica J, Wang Q, Massimi L, Witt H, Bender S, Pleier S, Cin H, Hawkins C, Beck C, von Deimling A, Hans V, Brors B, Eils R, Scheurlen W, Blake J, Benes V, Kulozik AE, Witt O, Martin D, Zhang C, Porat R, Merino D, Wasserman J, Jabado N, Fontebasso A, Bullinger L, Rücker F, Döhner K, Döhner H, Koster J, Molenaar JJ, Versteeg R, Kool M, Tabori U, Malkin D, Korshunov A, Taylor MD, Lichter P, Pfister SM, Korbel JO.  Cell. 2012, in press.

Bhattacharya N, Diener S, Idler IS, Barth TF, Rauen J, Habermann A, Zenz T, Moller P, Döhner H, Stilgenbauer S, Mertens D.   Non-malignant B cells and chronic lymphocytic leukemia cells induce a prosurvival phenotype in CD14+ cells from peripheral blood. Leukemia. 2011;25:722-726.

Nurse-like cells show deregulated expression of genes involved in immunocompetence.
Bhattacharya N, Diener S, Idler IS, Rauen J, Habe S, Busch H, Habermann A, Zenz T, Döhner H, Stilgenbauer S, Mertens D.;  Br J Haematol. 2011;154:349-356.

DNA damage-induced transcriptional program in CLL: biological and diagnostic implications for functional p53 testing.
Mohr J, Helfrich H, Fuge M, Eldering E, Buhler A, Winkler D, Volden M, Kater AP, Mertens D, Te Raa D, Döhner H, Stilgenbauer S, Zenz T.; Blood. 2011;117:1622-1632.

From pathogenesis to treatment of chronic lymphocytic leukemia.
Zenz T, Mertens S, Küppers R, Döhner H, Stilgenbauer S.; Nat Rev Cancer. 2010;10(1):37-50. (Review)

Highthroughput detection of nuclear factor-kappaB activity using a sensitive oligo-based chemiluminescent enzyme-linked immunosorbent assay.
Bhattacharya N, Sarno A, Idler IS, Fuhrer M, Zenz T, Döhner H, Stilgenbauer S, Mertens D.;  Int J Cancer. 2010;127:404-411.

Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the GCLLSG.
Stilgenbauer S, Zenz T, Winkler D, Bühler A, Schlenk RF, Groner S, Busch R, Hensel M, Dührsen U, Finke J, Dreger P, Jäger U, Lengfelder E, Hohloch K, Söling U, Schlag R, Kneba M, Hallek M, Döhner H.  J Clin Oncol. 2009;27(24):3994-4001.

Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up.
Zenz T, Kröber A, Scherer K, Häbe S, Bühler A, Benner A, Denzel T, Winkler D, Edelmann J, Schwänen C, Döhner H, Stilgenbauer S.;  Blood. 2008;112(8):3322-9.

Efficient nucleofection of primary human B cells and BCLL cells induces apoptosis, which depends on the microenvironment and on the structure of transfected nucleic acids.
Seiffert M, Stilgenbauer S, Döhner H, Lichter P.; Leukemia. 2007;21:1977-1983.

Allelic silencing at the tumor-suppressor locus 13q14.3 suggests an epigenetic tumorsuppressor mechanism.
Mertens D, Wolf S, Tschuch C, Mund C, Kienle D, Ohl S, Schroeter P, Lyko F, Döhner H, Stilgenbauer S, Lichter P.; Proc Natl Acad Sci U S A. 2006;103:7741-7746.

Automated array-based genomic profiling in chronic lymphocytic leukemia: Development of a clinical tool and discovery of recurrent genomic alterations.
Schwaenen C, Nessling M, Wessendorf S, Salvi T, Wrobel G, Radlwimmer B, Kestler HA, Haslinger C, Stilgenbauer S, Döhner H, Bentz M, Lichter P. Proc Natl Acad Sci U S A. 2004;101(4):1039-1044.

Genomic aberrations and survival in chronic lymphocytic leukemia.
Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M, Lichter P.; N Engl J Med. 2000;343:1910-6.

B2

Genomic and epigenetic mechanisms in CLL pathogenesis