Total RNA sequencing is performed on matched tissue and plasma samples within a human DLBCL cohort to identify (circulating) biomarkers, linked to phenotype, response, and prognosis. Complementary, cell-free RNA (cfRNA) is explored in a patient-derived DLBCL xenograft model, enabling step-by-step dissection of the circulating transcriptome in tumor-, immune-, and stromal cellderived fractions. Lastly, a multi-omics analysis will compare cfRNA with available cfDNA copy number and methylation patterns.