Mechanisms of Leukemogenesis

Project Leader

Priv.-Doz. Dr. rer. nat. Daniel Mertens

Biologe

Contact/Address

Department of Internal Medicine III
University Hospital of Ulm
Albert-Einstein-Allee 23
89081 Ulm
Germany

Department of Molecular Genetics (B061)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg

Phone (office): +49-(0)731-500-45870
Phone (lab): +49-(0)731-500-45828
Fax: +49-(0)731-500-45825

Homepage: www.mertens-lab.de

Lab Members (Ulm)

Marie Aurelia Bordas
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

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

Collaboration Partners

  • 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