Introduction: Non-Follicular Low-Grade B-Cell Lymphomas (LGBCL) are a subset of lymphomas that share overlapping clinical and histologic features. While most cases of LGBCL have an indolent course, some experience aggressive disease with no definitive biomarkers to identify aggressive cases at diagnosis. Significant advances have been made in the molecular classification of other lymphomas, yet molecular profiling and identification of mechanisms driving aggressive disease in LGBCL remain an unmet need. We previously used a multi-omic approach to characterize the molecular and immune landscapes of LGBCL tumors and identified a transcriptomic signature associated with cell proliferation and inferior overall survival (OS) in two independent cohorts (HR 7.82; 95% CI 2.4-25.4; p < 0.001 & HR 10.07; 95% CI 2.00-50.61; p = 0.005) and cases that transformed to DLBCL (Hopper et al., 2023). Here, we identify the oncoprotein DEK as a novel transcriptional regulator of this signature and use a functional genomic approach to further interrogate the role of DEK in B-cell lymphoma.