Inhibition of anti-apoptotic BCL2 proteins with BH3-mimetics is a highly promising novel strategy for the treatment of cancer, which is evidenced by the clinical success of Venetoclax in treating Chronic Lymphocytic Leukemia. In this project we will investigate the potential of BH3-mimetics for the treatment of Diffuse Large B-cell Lymphoma (DLBCL). The recent development of highly potent and selective inhibitors of BCL2, BCL-XL and MCL1 allows us to investigate the importance of these anti-apoptotic proteins for DLBCL and characterize pathways of apoptosis resistance. Thereby, this project will concentrate on pre-existing mechanisms of resistance, mechanisms of acquired resistance, and the influence of survival signalling provided by the microenvironment on the response to BH3-mimetics.