The novel immunocompetent Eµ-SOX11CCND1 mouse model phenotypically and molecularly resembles human mantle cell lymphoma

Purpose: Mantle cell lymphoma (MCL) remains incurable despite therapeutic advances, highlighting the need for improved preclinical models. Existing transgenic MCL mouse models have significant limitations, restricting their translational value. Experimental Design: We generated an immunocompetent MCL model by overexpressing the key oncogenic drivers SOX11 and CCND1 under the Eµ enhancer in C57BL/6 mice, aiming to replicate human MCL’s biological and pathological features. Results: Eµ-SOX11CCND1 mice developed lymphoma marked by clonal B1a cell expansion in lymphatic and extranodal tissues. Morphologic, immunophenotypic, and transcriptional profiling revealed strong similarity to human MCL, with pathway analysis confirming significant molecular overlap. Importantly, lymphoma cells could be adoptively transferred into wild-type recipients, enabling therapeutic testing within an intact immune system. Conclusions: The Eµ-SOX11CCND1 mouse represents a robust and biologically relevant model that faithfully recapitulates human MCL. Its immunocompetent nature and adoptive transfer capability make it a valuable model for studying disease mechanisms and evaluating novel therapeutic approaches for MCL patients.