Mantle cell lymphoma (MCL) is an uncommon mature B cell lymphoma which presents a clinical spectrum ranging from indolent to aggressive disease, with challenges in disease management and prognostication. MCL is characterized by significant genomic instability, affecting various cellular processes including cell cycle regulation, cell survival, DNA damage response and telomere maintenance, NOTCH and NF-kB/BCR pathways and chromatin modification. Recent molecular and next-generation sequencing studies unveiled a broad genetic diversity among the two molecular subsets, conventional (cMCL) and leukemic non-nodal (nnMCL), which may partially explain their clinical heterogeneity. Some asymptomatic and genetically stable nnMCL not requiring treatment at diagnosis may eventually progress clinically. Overall, high proliferation of tumor cells, blastoid morphology, TP53 and/or CDKN2A/B inactivation, and a high genetic complexity influence treatment outcome in cases treated with standard regimens. Emerging targeted and immunotherapeutic strategies are promising in refractory or relapsed cases and a few genetic and non-genetic determinants of refractoriness have been reported. This review summarizes recent advances in MCL biology, focusing on molecular insights, prognostic markers, and novel therapeutic approaches.
Copyright © 2024 American Society of Hematology.