Establishment and Characterization of a CCND1-Rearranged Non-Mantle Cell Lymphoma Cell Line and Patient-Derived Xenograft Model

Abstract The pathobiology of aggressive B-cell lymphomas with CCND1 rearrangements, distinct from Mantle Cell Lymphoma (MCL), presents a significant clinical challenge. These lymphomas are often difficult to diagnose and demonstrate resistance to standard immunochemotherapy, underscoring the urgent need for a deeper understanding of their underlying biology to develop more effective treatments. A major impediment to progress has been the lack of robust preclinical models that accurately reflect the complex genomics and clinical behavior of this disease. Here we directly address this critical gap by reporting the establishment and in-depth characterization of the first patient-derived cell line and a corresponding systemic patient-derived xenograft (PDX) model of a CCND1 -rearranged, non-MCL lymphoma with a rapidly fatal clinical course. Through a comprehensive multi-omics approach, we demonstrate that these novel in vitro and in vivo models faithfully recapitulate the primary tumor’s unique immunophenotype, its intricate genetic and transcriptional landscape, and its intrinsic resistance to conventional therapeutic agents.