SFB 684:  Molecular Mechnisms of Normal and Malignant Hematopoiesis

• Subject Area: Medicine ; Biology
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 13759457

Malignant diseases constitute one of the most challenging health problems in our society. In parallel to the increasing life expectancy the number of patients suffering form cancer is steadily increasing. To cope with this development, prevention and early detection as well as more effective therapies are urgently needed. These needs heavily rely on a better understanding of the biology and pathogenesis of malignant disorders that can be gained by novel techniques and molecular analyses that requires a close interaction between basic and clinical research.
Among the malignant disorders, leukaemias have always served as model diseases, in which the basic principles of pathogenesis and therapy were explored first. Acute leukaemias were the first diseases in which the efficacy of systemic chemotherapy could be demonstrated and chronic myeloid leukaemia was the first disease for which the relevance of a disease associated chromosomal aberration was demonstrated.
The special role of leukaemias at the cutting edge of cancer research results mainly from the easy accessibility of leukaemic cells that facilitates the analysis of the chromosomal and molecular pattern as well as the function of leukaemic cells in great detail.
The genes that are affected by leukaemia-associated translocations or mutations do not only play pivotal roles in leukaemogenesis but also the very same genes are frequently key players in normal hematopoietic development. In this way, studies of the transforming mechanisms of these genes will automatically touch on aspects of normal hematopoietic proliferation and differentiation.
Conversely, the study of normal hematopoietic development is of crucial importance to understand the process of leukaemogenesis.
It is the aim of this Collaborative Research Centre to dissect the molecular pathways and mechanisms that govern normal and malignant hematopoiesis. This will be accomplished by a close interaction between investigations focusing on single molecules or defined molecular pathways and analyses addressing the complexity of the disease and the physiological differentiation processes by using sophisticated model systems and patient material. To achieve this, a close cooperation between well-established basic researchers, junior group leaders and physician scientists is maintained. The Collaborative Research Centre has also access to patient material from the controlled clinical trials of the German AML Cooperative Group.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Human Chromatin Accessibility Complex and Chromosomal Instability (Project Head Becker, Peter Burkhard )
• A02 - Nuclear architecture in normal and malignant hematopoietic cell types studied by quantitative, correlative microscopy (Project Head Cremer, Thomas )
• A03 - Repair and Signaling of DNA Double-Strand Breaks in Normal and Malignant Hematopoiesis (Project Head Hopfner, Karl-Peter )
• A04 - The role and regulation of DNA methylation in normal and malignant hematopoiesis (Project Head Leonhardt, Heinrich )
• A06 - A transgenic mouse model for CALM/AF10 leukemias (Project Head Bohlander, Stefan Klaus )
• A07 - Characterization of the novel 'Human PBX1 Interacting Protein' (HPIP) and its role in normal and malignant hematopoiesis (Project Head Feuring-Buske, Michaela )
• A08 - Mechanisms of ParaHox gene induced leukemogenesis (Project Head Buske, Christian )
• A10 - Nucleolar targets of chemotherapy involved in cell cycle and growth control (Project Head Eick, Dirk )
• A11 - Validation of crucial signaling pathways in oncogene driven leukemias by an siRNA based in vivo approach (Project Head Duyster, Justus )
• A12 - Mechanisms of leukemic transformation by the receptor tyrosine kinase FLT3 in vitro and in vivo (Project Head Spiekermann, Karsten )
• A13 - The role of Notch-signaling in B cell development, activation and lymphomagenesis (Project Head Zimber-Strobl, Ursula )
• A14 - Molecular control of hematopoietic stem cell self renewal and differentiation (Project Head Schroeder, Ph.D., Timm )
• A15 - MALT1 Signaling in lymhomagenesis (Project Head Ruland, Jürgen )
• A17 - Epigenetic regulation of hematopoiesis (Project Head Schotta, Gunnar )
• A18 - The ubiquitin-editing enzyme A20 in B cell physiology and malignancy (Project Head Schmidt-Supprian, Marc )
• A19 - Functional analysis of histone variants during normal and malignant hematopoiesis (Project Head Hake, Sandra Brigitte )
• A20 - The role of the germinal center kinase family member TNIK in hematopoiesis and signaling (Project Head Kieser, Arnd )
• A21 - Functional Characterization of AML-associated Mutants of Nucleophosmin (Project Head Müller, Stefan )
• A22 - The effect of TRAIL on primary leukemia cells and leukemic stem cells (Project Head Jeremias, Ph.D., Irmela )
• Z01 - Central Administration (Project Heads Bohlander, Stefan Klaus ;  Hiddemann, Wolfgang )

• Applicant Institution: Ludwig-Maximilians-Universität München
• Participating University: Technische Universität München (TUM)
• Participating Institution: Helmholtz Zentrum München; Deutsches Forschungszentrum für Gesundheit und Umwelt; Max-Planck-Institut für Biochemie (MPIB)
• Spokespersons: Professor Dr. Stefan Klaus Bohlander, from 2/2010 until 11/2011; Professor Dr. Wolfgang Hiddemann, since 12/2011