BATF3: negative regulator of AP-1 - a new potential inhibitor of plasmacytic differentiation

• Applicant: Professor Dr. Martin-Leo Hansmann, since 4/2016
• Subject Area: Pathology
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250968982

Lymphoid malignancies represent a heterogeneous group of neoplasms, are increasing in incidence and are often of poor prognosis. The mechanisms involved in malignant transformation of mature B and T lymphocytes are still only partly understood. Previously, we compared gene expression profiles of Hodgkin´s lymphoma and anaplastic large cell lymphoma to their normal cellular counterparts (B and T cells, respectively) and found the transcription factor BATF3 to be significantly upregulated in the tumor cells of both entities. To assess a potential transformation capacity of BATF3 in lymphomagenesis, we retrovirally transduced murine mature T and B cells with a BATF3-encoding viral vector and transplanted each population into Rag-1 deficient recipients. Intriguingly, BATF3-expressing B lymphocytes readily induced B-cell lymphomas after characteristic latencies, whereas T-cell transplanted animals remained healthy throughout the observation time. Further analyses revealed overexpression of the germinal center B-cell marker BCL-6 in lymphoma samples. The proposed research project aims to clarify the potential role of BATF3 in B-cell lymphomagenesis and to understand the influence of BATF3 on B cells, especially during immune activation and germinal center formation. We want to establish a murine transplantation model to reveal the oncogenic potential of BATF3 and dissect the molecular interactions of BATF3 in gene-modified B cells. Finally, we want to validate identified molecular candidates in human B-cell lymphoma and elucidate the relevance of BATF3-expression in HL cell lines.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Dr. Sebastian Newrzela, until 3/2016