Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue--from (auto)antigen driven selection to the activation of NF-κB signaling.

Abstract

Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra- or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the "acquired lymphoid tissue". The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-κB signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future.

• Authors: YiAn Zhang, Zheng Wei, Jing Li, Peng Liu
• Journal: Science China. Life sciences (Sci China Life Sci) Vol. 58 Issue 12 Pg. 1246-55 (Dec 2015) ISSN: 1869-1889 [Electronic] China
• PMID: 26612043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens
• Autoantigens
• NF-kappa B
• Oncogene Proteins, Fusion

Topics

• Antigens (immunology)
• Autoantigens (immunology)
• Gene Expression Regulation, Neoplastic (immunology)
• Humans
• Lymphoma, B-Cell, Marginal Zone (genetics, immunology)
• Models, Immunological
• NF-kappa B (immunology)
• Oncogene Proteins, Fusion (genetics, immunology)
• Signal Transduction (immunology)
• Translocation, Genetic (immunology)