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-B 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. malt lymphoma, helicobacter pylori, chromosomal translocation, genetic alteration, NF-B Citation:Zhang YA, Wei Z, Li J, Liu P. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue-from (auto)antigen driven selection to the activation of NF-B signaling.

MALT lymphoma: epidemiology, clinical diagnosis and treatment

“…It was discovered that MALT lymphoma expresses high levels of a ligand (APRIL), a novel cytokine which is crucial in sustaining B-cell proliferation [ 13 ]. Also, H. pylori and H. pylori-specific T cells stimulate the macrophages to produce APRIL [ 14 ]. In addition, H. pylori can translocate the CagA protein directly into B-cells resulting in extracellular signal-regulated kinase activation and Bcl-2 expression up-regulation, leading to apoptosis inhibition [ 15 ].…”

Value of Maximum Standard Uptake Value as a Positron Emission Tomography/Computed Tomography Index in the Diagnosis and Prognosis of Patients with Gastric Cancer

“…The pathological type of the former is mainly diffuse large B-cell lymphoma, and the latter is gastric. Mucosa-associated lymphoid tissue lymphoma is predominant [29]. Primary gastric lymphoma mainly in ltrates in the mucosa.…”

Mucosa-associated lymphoid tissue lymphoma with unusual18F-FDG hypermetabolism arising at the colorectal anastomosis

“…The functional CARD11 associates with BCL10 and MALT1 to form an active CBM signalosome, which activates inhibitor of NF-κB kinase (IKK) and subsequently triggers activation of the NF-κB pathway (Figure 9A )[ 6 ]. In BCR-independent NF-κB pathways, chromosomal abnormalities facilitated by reactive oxygen species (ROS), play a significant role in the genesis of MALT lymphoma[ 7 ]. Occurring in 25%-60% of gastrointestinal MALT lymphomas, chromosomal translocation t(11;18)(q21;q21) is the most common genetic abnormality, leading to the linkage of BIRC3 gene on chromosome 11 and MALT1 gene on chromosome 18[ 8 ].…”