SOX11 in Mantle Cell Lymphoma - Novel Tools for Diagnostic, Prognostic and Functional Investigations

Abstract: The goal of biomarker discovery is to identify disease defining molecules, which could be used to improve early detection and/or to predict survival and response to treatment. This thesis is about the transcription factor SOX11, a protein discovered in the context of mantle cell lymphoma in 2008, which shows great potential to be used as a clinical relevant biomarker. The aim of this thesis is to extend the use of SOX11, by providing novel tools for research applications as well as for diagnosing and stratifying mantle cell lymphoma patients. The results from my studies are presented in four papers in the thesis. First, we developed a monoclonal SOX11 antibody for the diagnostic classification of mantle cell lymphoma patients. Using this antibody, we showed that the expression of SOX11 correlates with patient survival and that inclusion of either SOX11 or p53 into the well-established prognostic index MIPI improve patient classification. To understand the growth regulatory role of SOX11, DNA binding sites and interacting protein partners needs to be identified. We continued to generate and assess the specificities of SOX11 targeting antibodies for immunoprecipitation assays, with the aim to get further insight into SOX11 signaling pathways using chromatin immunoprecipitation coupled to next generation sequencing or co-immunoprecipitation coupled to mass spectrometry. Finally, we investigated the epigenetic regulation of SOX11 and demonstrate the ability of re-expression using histone deacetylase inhibitors. In conclusion, this thesis presents novel tools, including the developed SOX11 antibody and the improved prognostic index for stratifying mantle cell lymphoma patients. Additionally, the developed SOX11 antibody has expanded our research applications to include flow cytometry and immunoprecipitation assays.