Lymphoid malignancies, including mantle cell lymphoma (MCL) and Burkitt’s lymphoma (BL), pose significant challenges in treatment due to their complex molecular mechanisms. The transcription factor SOX11 is known for its role in neuronal differentiation but has been found to be aberrantly expressed in lymphomas. While its oncogenic function in MCL has been established, its role in BL remains unclear. Recent research suggests that SOX11 may influence sensitivity to high-dose cytarabine (ara-C), a key chemotherapy agent in MCL treatment, through its interaction with the SAMHD1 protein, which is implicated in drug resistance. This master’s thesis explores the structural and functional implications of the SOX11-SAMHD1 interaction in lymphoid malignancies using computational and transcriptomic approaches. The study aims to predict the binding interface between SOX11 and SAMHD1, analyze its impact on SAMHD1 tetramerization, and investigate associated gene expression patterns across different lymphomas. The research will leverage artificial intelligence-assisted molecular docking, mass spectrometry-based proteomics, and transcriptomic analyses to provide insights into the biological significance of this interaction. The methodology involves computational structural modeling using AlphaFold and docking simulations with HADDOCK and ClusPro. Mass spectrometric data from SOX11 co-immunoprecipitation experiments will be analyzed using MaxQuant and Perseus, with interaction networks built through STRING. Transcriptomic analysis of BL datasets from The Cancer Genome Atlas (TCGA) will be conducted using RNA-seq analysis tools such as DESeq2 and EdgeR. Additionally, cross-linking immunoprecipitation assays will be employed to study the impact of SOX11 on SAMHD1 tetramerization. The findings of this study will contribute to a deeper understanding of SOX11’s non-canonical functions in lymphoma biology. By identifying synthetic vulnerabilities linked to SOX11 expression, this research may provide a foundation for developing novel therapeutic strategies and improving the efficacy of existing treatments in lymphoid malignancies. The project will be conducted at the Karolinska Institute under the supervision of experts in pathology and lymphoma research, ensuring rigorous experimental design and analysis. This study is expected to have significant implications for cancer research by offering new perspectives on the molecular interactions governing lymphoma progression and drug resistance. Ultimately, it aims to enhance therapeutic targeting in lymphoid malignancies, paving the way for more effective and personalized treatment strategies.