SFB 1074:  Experimental Models and Clinical Translation in Leukemia

• Subject Area: Medicine
• Term: from 2012 to 2024
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 217328187

In recent years, there has been enormous progress in characterizing genetic drivers in leukemogenesis, followed by the successful clinical development of molecular therapies. Collaborative Research Center (CRC) 1074 has anticipated and accompanied this development from the very beginning. CRC 1074 has aimed at bridging basic, translational and (pre)clinical research in the field of leukemia, focusing on translating insights into the pathogenesis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) into new therapies.The structure of CRC 1074 consists of two closely interacting Project Groups: Group A projects with the expertise in experimental models of leukemogenesis, and Group B projects focusing on translational / preclinical leukemia research. Here, CRC 1074 has the privilege to benefit from most visible clinical research in leukemia and unique biobanks of the national leukemia study groups located at Ulm University, belonging to the largest clinically and molecularly annotated collections worldwide. The individual projects are complemented by two core projects, the Bioinformatics/Single-Cell Sequencing Core (Z1) and the Mass Spectrometry and Proteomics Core (Z3). In the grant renewal proposal, seven new principal investigators have been integrated, five of them being young female scientists with an outstanding record, at different stages of their career. Furthermore, CRC 1074 has integrated two research groups from the German Cancer Research Center in Heidelberg, and one group from Charité University Medicine Berlin, based on their specific expertise and on already long-standing collaborations.We expect that a third funding period of CRC 1074 will further successfully strengthen the international visibility of basic and translational leukemia research at Ulm University and continue to provide major scientific contributions. The invaluable resources of CRC 1074 will facilitate translating research findings into clinical practice and ultimately improve care of patients with leukemia.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - The contribution of mechanisms of aging of HSCs to leukemia initiation and progression (Project Head Geiger, Hartmut )
• A03 - Notch signaling as a novel target of AML/ETO (Project Heads Geiger, Hartmut ;  Oswald, Franz )
• A04 - Dissecting of the function of the “Lymphoid enhancer-binding factor 1” (Lef1) in acute myeloid leukemia (Project Head Buske, Christian )
• A06 - The role of homeobox genes in erythroid leukemia (Project Head Feuring-Buske, Michaela )
• A09 - Role of B cell receptor signaling and acquired immunoglobulin gene changes in the development of chronic lymphocytic leukemia (CLL) (Project Heads Hobeika, Elias ;  Jumaa, Hassan )
• A10 - Investigating the crosstalk between pre-BCR and IL-7R signaling in B-cell precursor acute lymphoblastic leukemia (Project Head Jumaa, Hassan )
• B01 - Genomic instability, disease evolution and rational treatment development in CLL mouse models (Project Heads Jebaraj, Billy ;  Müller, Annika ;  Stilgenbauer, Stephan )
• B02 - Mechanisms of CLL progression and Richter transformation in patients with CLL treated with agents targeting BTK and BCL2 (Project Heads Döhner, Hartmut ;  Mertens, Daniel ;  Stilgenbauer, Stephan )
• B03 - Molecular and functional characterization of cooperating events in acute myeloid leukemia with NPM1 mutation (Project Heads Bullinger, Lars ;  Döhner, Konstanze )
• B06 - Multi-targeting and identification of synergistic activities to overcome therapy resistance in ALL (Project Heads Debatin, Klaus-Michael ;  Meyer, Lüder Hinrich )
• B08 - The role of deubiquitinating enzyme USP7 in the pathogenesis and treatment of acute myeloid leukemia (Project Head Krönke, Jan )
• B09 - Causes and consequences of epigenetic disturbances in T-prolymphocytic leukemia (Project Heads Siebert, Reiner ;  Wiehle, Laura )
• B10 - Genetic and epigenetic characterization of chronic lymphocytic leukemia with translocations involving the immunoglobulin loci (Project Heads Mottok, Anja ;  Siebert, Reiner )
• B11 - Novel oncogenes in complex karyotype acute myeloid leukemia (Project Head Plass, Christoph )
• B12 - Dissecting AML treatment response to FLT3 inhibitors by single-cell sequencin (Project Heads Döhner, Konstanze ;  Rippe, Karsten )
• Z01 - Bioinformatics core - semantic knowledge fusion and non-standard optimization - Next Generation Sequencing core (Project Heads Kestler, Hans A. ;  Rippe, Karsten )
• Z02 - Central Tasks (Project Head Döhner, Hartmut )
• Z03 - Qualitative and quantitative proteomics for a comprehensive picture of protein dynamics in leukemia (Project Head Wiese, Sebastian )

Completed projects

• A02 - Dissecting the role of Mixed-Lineage-Leukemia 5 (MLL5) in the DNA damage response and its potential effects on leukemogenesis (Project Head Fehling, Hans-Jörg )
• A05 - Characterization of regulatory and target pathways of microRNAs downstream of the leukemogeneic Hoxa9/Meis1 axis (Project Heads Kuchenbauer, Florian ;  Rouhi, Arefeh )
• A07 - Role of EZH2 in B-lymphoid and myeloid leukemogenesis (Project Head Wirth, Thomas )
• A08 - Mechanistic basis of CLL resistance to targeted tumor therapy in a pathophysiologically relevant cellular context: role of Rho GTPases and phospholipase C-y2 (Project Head Gierschik, Peter )
• B04 - Functional analysis of recurrent deletions of chromosomal band 3p14.1-p13 in acute myeloid leukemia (Project Head Gaidzik, Verena )
• B07 - Attenuated oncolytic measles virus against ALL of childhood: preclinical proof-of-principle and molecular mechanisms (Project Head Beltinger, Christian )

• Applicant Institution: Universität Ulm
• Participating Institution: Charité - Universitätsmedizin Berlin; Deutsches Krebsforschungszentrum (DKFZ)
• Spokesperson: Professor Dr. Hartmut Döhner