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Abstract

Diffuse large B-cell lymphoma (DLBCL), the most prevalent aggressive non-Hodgkin lymphoma, exhibits substantial molecular heterogeneity and arises from germinal center or post-germinal center B cells through recurrent genetic and epigenetic dysregulation of critical signaling pathways. Aberrations involving BCL6, MYC, MYD88, and components of B cell receptor and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B) signaling play central roles in lymphomagenesis, treatment resistance, and clinical outcomes. Gene expression profiling has defined major molecular subgroups in DLBCL, including germinal center B cell–like and activated B cell–like tumors, that show distinct pathogenesis and prognosis. High-risk entities, such as double- and triple-hit lymphomas, remain therapeutically challenging despite advances in immunochemotherapy. Recent progress in molecular diagnostics and targeted therapies, including immune checkpoint inhibition, Bruton tyrosine kinase inhibitors, B-cell lymphoma 2 (BCL2) antagonists, and Chimeric antigen receptor-T cells, has expanded precision-based treatment strategies. This review summarizes advances in understanding the molecular mechanisms of DLBCL and emphasizes emerging therapeutic approaches informed by genomic and microenvironmental discoveries.

Article Type

Review

First Page

1141

Last Page

1149

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