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Department of Pathology

 

Professor Ming-Qing Du from the University of Cambridge conducted a pivotal review of the pathogenesis of extranodal marginal zone lymphoma (EMZL). This study, published in Blood, sheds new light on the molecular mechanisms underlying EMZL and provides a framework for future research.

 

EMZL, a type of B-cell lymphoma, arises in mucosa-associated lymphoid tissue (MALT) and is driven by chronic inflammation due to microbial infection and autoimmunity. This comprehensive review explores how immune responses at different anatomical sites create a distinct microenvironment that fosters the evolution of malignant B cells.

 

Key findings from the study include:

  • Site-Specific Genetic Profiles: EMZL at different anatomical sites exhibits unique oncogenic mutations and translocations, such as the role of BCL10 and MALT1 translocations in gastric EMZL and GPR34 activation in salivary gland EMZL.

  • T-Helper Cell Influence: The study highlights the significant role of T-helper cells in promoting B-cell malignancy, particularly in gastric and thyroid EMZL, where impaired co-inhibitory interactions lead to unchecked immune stimulation.

  • NF-κB Pathway Activation: Genetic alterations such as TNFAIP3 (A20) deletion in ocular adnexal EMZL reinforce the importance of NF-κB dysregulation in lymphoma development.

  • Autoimmune Associations: EMZL arising in the thyroid and salivary glands are closely linked to Hashimoto’s thyroiditis and Sjögren’s syndrome, respectively, demonstrating how chronic inflammation paves the way for lymphomagenesis.

 

“This review provides critical molecular insights that bridge chronic inflammation to lymphoma development. Understanding these pathways clarifies disease progression and offers potential targets for therapeutic intervention,” said Professor Ming-Qing Du, the study’s lead author.

 

The findings of this study may pave the way for more targeted treatment strategies and novel therapeutic approaches for EMZL patients. Researchers and clinicians can explore precision medicine approaches to combat this form of lymphoma by deepening the understanding of site-specific genetic drivers and immune interactions.

For more information, the entire study is available at https://doi.org/10.1182/blood.2024025794.