B cell development is dependent on functional DNA repair and thus deficiencies within these pathways promote lymphomagenesis and are frequently found in high-risk B cell lymphomas. In this project, mantle cell lymphoma (MCL) will serve as a blueprint, as alterations in key DNA repair pathways are typically present in up to 50% of cases without being therapeutically exploited to date. We will perform functional and longitudinal profiling of genome instability in a high-risk relapse/refractory MCL cohort and mechanistically dissect the kinase-driven DNA repair pathways in order to identify and validate vulnerabilities of rewired DNA repair signaling.
PRINCIPAL INVESTIGATOR
Department I of Internal Medicine
University Hospital of Cologne
Kerpener Straße 62
50937 Cologne
Max Planck Institute for Biology of Ageing
Joseph-Stelzmann-Strasse 9b
50931 Cologne
Project Interactions
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A01
Using autochthonous mouse models of aggressive lymphoma to systematically distill actionable vulnerabilities
Prof. Dr. med. Hans Christian Reinhardt -
B01
LYN kinase as a key regulator in the microenvironmental niche of B cell lymphoid tumors
Prof. Dr. med. Michael Hallek, Dr. rer. nat. Phuong-Hien Nguyen -
C03
Proteogenomic characterization of mantle cell lymphoma
Prof. Dr. med. Reinhard Büttner, Prof. Dr. med. Thomas Oellerich -
C05
Characterization of Richter-transformed lymphoma and genomic instability as a potential vulnerability in 17p-deleted lymphomas
Prof. Dr. med. Björn Chapuy, Prof. Dr. med. Barbara Eichhorst