EMZL at various sites: learning from each other

作者：Ming‐Qing Du · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2024025794 · 被引用次数：15 · 研究领域：Immune Cell Function and Interaction、Lymphoma Diagnosis and Treatment、NF-κB Signaling Pathways

ABSTRACT: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL) invariably develops from a background of chronic inflammatory disorder caused by a diverse chronic microbial infection and/or autoimmunity, depending on the site. These chronic inflammatory/autoimmunity disorders trigger innate and acquired immune responses, generating a unique microenvironment at each site that drives clonal evolution of B cells, their expansion, and eventual malignant transformation. At a molecular level, this involves temporal and spatial acquisition of cooperative oncogenic events by dysregulated immune responses and somatic genetic changes. Although these events are not yet fully characterized, EMZL at several sites shows distinct genetic profiles and molecular insights, bridging the pathologic process to lymphomagenesis. For example, gastric EMZL, particularly those lacking a BCL10 or MALT1 translocation, critically depends on T-helper cell signals produced by immune responses to Helicobacter pylori infection. Likewise, thyroid EMZL may also involve exaggerated T-cell help because of highly frequent inactivating mutations in TET2, CD274 (programmed cell death 1 ligand 1), and TNFRSF14, which impede the coinhibitory interactions between the neoplastic B- and T-helper cells, thus releasing T-cell help. Ocular adnexal EMZL shows frequent TNFAIP3 (A20) mutation/deletion that significantly associates with expression of autoreactive IGHV4-34 B-cell receptor, emphasizing it...