B-cell lymphoma: Advances in pathogenesis, diagnosis, and targeted therapies

Abstract

B-cell lymphomas (BCL) represent a heterogeneous group of blood cancers originating from B-lymphocytes, characterized by diverse clinical manifestations and molecular characteristics. This review highlights recent progress in understanding their pathogenesis, diagnostic approach advancements, and therapeutic strategies developments. Key genetic alterations such as chromosomal translocations (e.g., t(14;18), MYC rearrangements), mutations in tumor suppressor genes like TP53, and disruptions in critical signaling pathways including B-cell receptor (BCR), NF-κB, PI3K/AKT, and JAK/STAT are central to disease development. Additionally, non-coding RNAs, especially microRNAs, play crucial regulatory roles in lymphomagenesis. Innovations in diagnostics, such as liquid biopsy technologies using cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), have enhanced early detection, disease monitoring, and prognostication. Concurrently, molecular biomarkers and emerging classifiers improve risk assessment and guide treatment decisions. Treatment approaches have evolved beyond traditional chemotherapy and radiotherapy. Targeted therapies such as monoclonal antibodies, kinase inhibitors, bispecific antibodies, and CAR-T cell therapies have shown particular promise in relapsed or refractory cases. Stem cell transplantation remains a valuable option for select patients. Additionally, novel agents targeting epigenetic mechanisms and tumor angiogenesis are under active investigation. This review underscores both the significant advancements and ongoing challenges, such as therapy resistance and adverse effects. The integration of molecular diagnostics with precision-targeted and immune-based therapies is key to advancing personalized care. Future research should aim to characterize tumor heterogeneity better and optimize therapeutic strategies to improve outcomes for patients with B-cell lymphomas.