Pathogenesis of Gastric MALT Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is a heterogeneous form of a B-cell non-Hodgkin's lymphoma with extranodal location. In the view of molecular biology, there are two types of MALT lymphoma: translocation-negative MALT lymphoma and translocation-positive MALT lymphoma. The pathogenesis of translocation-negative MALT lymphoma is driven by an active immune response to Helicobacter pylori infection. Thismost probably underscores the tumor cell survival and proliferation, and thus determines their response to Helicobacter pylorieradication. The oncogenic products of t(1;14) (p22;q32)/CL10-IGH, t(14;18)(q32;21)/IGH-MALT1 and t(11;18)(q21;q21)/API2-MALT1, found in translocation-positive MALT lymphoma, are all potent activators of the NF-kappaB activation pathway. They activate the canonical NF-kappaB activation pathway, and also potentially trigger directly and /r indirectly activation of the non-canonical NF-kappaB pathway. Inactivation of the global NF-kappaB inhibitor A20 also impacts upon multiple signaling pathways leading to NF-kappaB activation and thus potentially exacerbates the effect of stimulation of surface receptors. This review discusses the recent advances in the molecular pathogenesis of MALT lymphoma, and explores how the above genetic abnormalities cooperate with immunological stimulation in the development of lymphoma.

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication.

BCL10 expression and chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma / 中华皮肤科杂志

Objective To study the expression of BCL10 and associated chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma (PCMZL). Methods Tissue specimens were collected from 17 patients with PCMZL. Immunohistochemistry was used to detect the expression of BCL10. Fluorescence in situ hybridization (FISH) was performed to examine the presence of API2-MALT1 fusion gene and chromosomal aberration in BCL10, MALT1 as well as IgH genes in these cases. Results Of these patients,94.1% (16/17) expressed BCL10 protein. The cytoplasmic expression of BCL10 was observed in 64.7% (11/17) of the patients, and nuclear expression in 29.4% (5/17). As shown by FISH test, neither API2-MALT1 fusion gene nor chromosomal aberration in BCL10, MALT1 or IgH genes was present in these patients. Conclusions Compared with MALT lymphomas originating from tissues other than skin, PCMZL is uncommonly associated with chromosomal abnormalities; it is possible that there are unknown factors contributing to its tumorigenesis. Nuclear BCL10 is unrelated to the presence of chromosomal aberration in BCL10, MALT1 or IgH genes. Further follow-up is required to clarify the association between nucle ar BCL10 and poor prognosis of PCMZL.

Lymphomas with CARMA1, BCL10, MALT1 and NF-?B signaling pathway / 中国癌症杂志

CARMA1, BCL10 and MALT1 are lymphocyte-specific signaling molecules of NF-?B pathway.The abnormalities of those molecules such as gene mutation, rearrangement, translocation or amplification often connect with the lymphoma genesis. This article reviewed the physiological function of those molecules and the relationship between genetic abnormalities and lymphoma genesis, also with present target-treatment research and new gene medicine development.

Chromosome translocation t (11;18) and expression of BCL10 protein in gastric mucosa-associated lymphoid tissue lymphoma / 中华消化杂志

Objective To detect chromosome translocation t (11;18)(q21;q21) and expression of BCL10 protein in gastric mucosa associated lymphoid tissue (MALT) lymphoma. Methods We, combining clinical and pathological data, detected API2 MLT fusion by reverse transcriptase polymerase chain reaction (RT PCR)as well as the expressions of BCL10 protein and Ki 67 by immunohistochemistry in cases of gastric MALT lymphoma and follicular gastritis (FG) and analyzed the relationships among them. Results API2 MLT fusion was detected in three cases (2 low grade and 1 low to high grade) out of 14 cases of gastric MALT lymphoma, and no in 8 cases of FG. BCL10 protein was weakly expressed in cytoplasm of B cells of germinal center in lymph follicles of FG; but abundantly in cytoplasm of tumor cells in gastric MALT lymphoma; 42.5% of the latter showed weak expression in nucleus. The expression of Ki 67 was significantly higher in low to high and diffuse large B cell lymphoma cases than in low grade cases( P 0.05), the frequency of nuclear expression of BCL10 increased with the increased expression of Ki 67. Conclusions Both API2 MLT fusion and BCL10 nuclear expression are associated with transformation of gastric MALT lymphoma from LG to HG. RT PCR technique used to detect API2 MLT fusion may be an important tool in identification of t(11;18)(q21;q21).