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Mechanisms of Leukemogenesis

Contact/Address

PD Dr. rer. nat Daniel Mertens

Department of Internal Medicine III

University of Ulm

Albert-Einstein-Allee 23

89081 Ulm

Germany

 

Department of Molecular Genetics (B061)

Deutsches Krebsforschungszentrum

Im Neuenheimer Feld 280

69120 Heidelberg

 

E-Mail: daniel.mertens[at]uniklinik-ulm.de, d.mertens[at]dkfz.de

Homepage: www.mertens-lab.de

Phone (office):
Phone (lab):
Fax:

0049+(0)731-500-45870
0049+(0)731-500-45828
0049+(0)731-500-45825

 

Project Leader

PD Dr. rer. nat. Daniel Mertens

 

Lab Members (Ulm)

Dr. rer. nat. Sabrina Kugler

Karin Müller

Ellen Scheidhauer

Dr. rer. nat. Deyan Yosifov


Lab Members (Heidelberg)

Katharina Filarsky

Dr. rer. nat. Irina Idler

Dr. rer. nat. Michaela Reichenzeller

Christine Wolf

Research Fields

We are interested in the molecular mechanisms that cause leukemias and lymphomas. The scope of our research projects ranges from the elucidation of an epigenetic suppressor mechanism to the characterization of leukemogenic signal transduction pathways in the malignant cells.


How does the microenvironment support leukemic cells?

Malignant cells of patients suffering from B-cell chronic lymphocytic leukemia (B-CLL) accumulate in the lymphatic organs and peripheral blood and finally result in the failure of the immune system. However, if the malignant cells are cultured in vitro, they rapidly undergo apoptosis unless they are supported by non-malignant stroma cells. This suggests an intimate interaction of the leukemia cells with their microenvironment and an essential dependence on survival signals from the supporting cells. In a systematic approach, we want to characterize the delicate interplay of these anti-apoptotic signals which have been discovered to date. Even though each of these signals prolongs the life of CLL cells in vitro, none of them can alone substitute the anti-apoptotic effect that the stromal cells have on the leukemic cells in vitro. If we are able to describe this crucial balance of supporting signals and identify its central nodes, these could be directly targeted in the patients using low but effective doses of compounds, some of which are already clinically established.

Grants/Funding

  • Virtuelles Helmholtz Institut „Resistance Mechanisms of Leukemia Cells“
    (www.leukemia-resistance.de)
  • BMBF Netzwerk „CancerEpiSys“ (www.cancerepisys.org)
  • Wilhelm Sander Stiftung für Krebsforschung
  • Medizinische Fakultät Universität Ulm, Abteilung Innere Medizin III
  • Helmholtz Nachwuchsgruppenförderung (Juniorgruppe am DKFZ)
  • EU Marie Curie Training Network
  • Deutsche José Carreras Leukämie-Stiftung

Representative Publications

(a comprehensive list is available at www.mertens-lab.de)
 

Bhattacharya, N., M. Reichenzeller, M. Caudron-Herger, S. Haebe, N. Brady, S. Diener, M. Nothing, H. Dohner, S. Stilgenbauer, K. Rippe and D. Mertens (2014). "Loss of cooperativity of secreted CD40L and increased dose-response to IL4 on CLL cell viability correlates with enhanced activation of NF-kB and STAT6." Int J Cancer, 136(1):65-73, IF 6.198

Allegra, D., Bilan, V., Garding, A., Döhner, H., Stilgenbauer, S., Kuchenbauer, F., Mertens, D. (2013), Defective DROSHA processing contributes to downregulation of miR-15/-16 in chronic lymphocytic leukemia, Leukemia, 28(1):98-107, IF 10.164

Garding, A., Bhattacharya, N., Claus, R., Ruppel, M., Tschuch, C., Filarsky, K., Idler, I., Zucknick, M., Caudron-Herger, M., Oakes, C., Fleig, V., Keklikoglou, I., Allegra, D., Serra, L., Thakurela, S., Tiwari, V.,  Weichenhan, D., Benner, A., Radlwimmer, B., Zentgraf, H., Wiemann, S., Rippe, K., Plass, C., Döhner, H., Lichter, P. Stilgenbauer, S., Mertens, D. (2013), Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is linked to the in cis downregulation of a gene cluster that targets NF-kB, PLOS Genetics, 9(4): e1003373, IF 8.694

Garding, A., Bhattacharya, N., Haebe, S., Mueller, F., Weichenhan, D., Idler, I., Ickstadt, K., Stilgenbauer, S., Mertens, D. (2013) TCL1A and ATM are coexpressed in chronic lymphocytic leukemia cells without deletion of 11q, Haematologica, 98(2):269-73, IF 6.416

Zenz, T., D. Mertens, R. Kuppers, H. Dohner and S. Stilgenbauer (2010). From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 10:1: 37-50, IF 29.538

Collaborations

  • Prof. Dr. rer. nat. P. Lichter, DKFZ, Heidelberg
  • Prof. Dr. med. Stephan Stilgenbauer
  • Dr.rer.nat. Martina Seiffert, DKFZ, Heidelberg
  • PD. Dr.rer.nat. Karsten Rippe, DKFZ, Heidelberg
  • Prof. Dr. rer. nat. Thomas Höfer, BioQuant, Heidelberg
  • Dipl. Stat. A. Benner, DKFZ, Heidelberg

Forschungsbereiche

Molecular Genetics of Myeloid Leukemia
Prof. Dr. Konstanze Döhner / Prof. Dr. Lars Bullinger

Molecular Genetics of Myeloproliferative Disorders
Dr. Frank Stegelmann / Prof. Dr. Konstanze Döhner

Molecular Pathogenesis and Progression of Lymphoproliferative Disorders
Prof. Dr. Stephan Stilgenbauer

Mechanisms of Leukemogenesis
PD Dr. Daniel Mertens

Molecular Pathogenesis and Prognostic Markers in Monoclonal Gammopathies
PD Dr. Christian Langer

Tumor Immunology Group (TIG)
Prof. Dr. Jochen Greiner

Haemostaseology
PD Dr. Christian Langer
 

Molecular Hematopoiesis
Dr. Dr. Florian Kuchenbauer

 

Emmy Noether Research Group

Dr. Jan Krönke

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