Elucidation of the functional role of BCL10 mutations in diffuse large b-cell lymphoma

• Applicant: Dr. Sebastian Scheich
• Subject Area: Hematology, Oncology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 420153849

Lymphomas are a heterogenous group of diseases and are classified as indolent and aggressive lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of aggressive lymphomas. Recently published studies identified four DLBCL subgroups based on their genomic profiles. In the BN2-subtype over one third of all patients had BCL10 mutations. However, their functional role remains unclear. Within the proposed project we aim to elucidate the functional role of BCL10 gain-of-function mutations. Therefore, we will introduce BCL10 mutations in different DLBCL cell lines to investigate the effect on NF-κB signaling in those cells. Furthermore, we will investigate the mechanisms and signaling networks of cells with BCL10 mutations aiming to understand why they have a superior survival compared to wildtype cells. Ultimately, we plan to perform multi-drug screens to find synergistic drug combinations for DLBCL patients with BCL10 mutations. Taken together, the main objective of the proposed project is to mechanistically characterize the role of a relevant mutation in DLBCL patients in order to improve future therapeutic approaches.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Louis Staudt, Ph.D.