Expression of A20 in patients with systemic lupus erythematosus / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the expression and regulation of A20 in healthy individuals and the patients with systemic lupus erythematosus (SLE).METHODS:The expression levels of A20, NF-κB, MALT1, and MALT1V1 in peripheral blood mononuclear cells ( PBMC) of the patients with SLE ( including 2 cases with scleroderma, 1 case with rheumatoid arthritis, and 1 case with lymphoma) were analyzed by real-time PCR.RESULTS:A significantly lower A20 expression level was found in the PBMC from SLE group compared with the healthy controls, while the expression levels of MALT1 and NF-κB were also decreased.In addition, no significant correlation between A20 and NF-κB expression levels in healthy group was observed, but a positive correlation was found in SLE group ( P<0.05) .A significant positive corre-lation between MALT1 and NF-κB expression levels in healthy group ( P<0.05) was observed, and no significant correla-tion was found in SLE group.The expression level of MALT1V1 in SLE group was significantly lower than that in healthy control group, and there was a positive correlation between A20 and MALT1V1 in healthy volunteers (P<0.01), but that did not exist in SLE group.CONCLUSION: The characteristics of the expression pattern of MALT1-A20-NF-κB in the SLE patients were presented.Lower level of A20 expression was found in the SLE patients, in particular with other autoim-mune disease or lymphomas, indicating the lower immune tolerance in SLE.The positive correlation of A20 and NF-κB may relate to positive regulation of MALT1.

Clinicopathologic Study of Chromosomal Aberrations in Ocular Adnexal Lymphomas of Korean Patients

PURPOSE: The incidence and clinical correlation of MALT1 translocation and chromosomal numerical aberrations in Korean patients with ocular adnexal mucosa associated lymphoid tissue (MALT) lymphoma have not yet been reported. We investigated the incidence and clinicopathologic relationship of these chromosomal aberrations in ocular adnexal MALT lymphomas in a Korean population. METHODS: Thirty ocular adnexal MALT lymphomas were investigated for the t(11;18) API2-MALT1, t(14;18) IgH-MALT1 translocations and chromosomes 3 and 18 aneuploidies using fluorescence in situ hybridization. Patient medical records were reviewed retrospectively for information on demographics and clinical characteristics, including treatment response. RESULTS: The MALT1 gene rearrangement was found in one out of 30 cases. The t(14;18) IgH-MALT1 translocation was demonstrated in only one case (3.3%), and the t(11;18) API2-MALT1 translocation was not found in any of the cases. Trisomy 3 was observed in three ocular adnexal MALT lymphomas (10.0%), and five cases showed trisomy 18 (16.7%). Translocation positive cases also showed trisomy 18. One case of tumor relapse showed trisomy 18 only in the recurrent biopsies. There were no statistically significant correlations between chromosomal aberrations and clinical characteristics and treatment responses. CONCLUSIONS: Translocations involving the MALT1 gene are not common in Korean ocular adnexal MALT lymphomas. The t(14;18) translocation was detected in only one out of 30 cases, and the t(11;18) translocation was not found at all. Furthermore, the chromosomal aberrations found in this study had no prognostic implications.

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.

Clinical Significance of MALT1 Gene Detection in Extra-nodal B Cell Lymphoma / 中国肿瘤临床

Objective: To investigate the relationship between MALT1 mRNA expression in extranodal B cell lymphoma and the pathogenesis of MALToma and DLBCL, and to explore the effect of MALT1 mRNA expression on the clinicopatho-serve the expression of Bcl-2 and Ki-67 in 106 samples of extranodal B cell lymphoma.The mRNA of MALT1 was detected by RT-PCR.Clinicopathological data were reviewed.Follow-up and statistical analysis were performed.Results: Expression of MALT1 mRNA was statistically different between the cases with lymph node metastasis and those without lymph node mestastasis, and between staging Ⅰ-Ⅱ cases and stage Ⅲ-Ⅳ cases, The expression of MALT1 mRNA in cases with posi-tive expression of MALToma, DLBCL, and Bcl-2 was higher than in those without expression of the three indices (P<0.05).However, no significant difference was found in MALT1 mRNA expression between cases with Ki-67≥30% and those with Ki-67<30% (P>0.05).MALT1 mRNA-positive cases showed a worse survival status than MALT1 mRNA-negative cases (P<0.05).Conclusion: Expression of MALT1 gene is different between MALToma and DLBCL.Inhibition of apoptosis by Bcl-2 overexpression caused by activation of NF-κB may lead to the pathogenesis of MALToma and DLBCL.The expression of MALT1 mRNA is associated with the types of lymphoma, involvement of lymph node, stage of lymphoma, and patient sur-vival.The expression of MALT1 gene may be associated with poor prognosis of MALToma and DLBCL.

A case of an API2-MALT1 translocation-positive gastric MALT lymphoma resistant to Helicobacter pylori eradication / 대한내과학회지

About 90% of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas are strongly related to Helicobacter pylori infection. The eradication of the H. pylori by antibiotics leads to complete regression of the gastric MALT lymphoma in 80%of cases, and this is currently recommended as the first-line treatment for this tumor. However, no standard treatment for H. pylori-negative and H. pylori-eradication-resistant gastric MALT lymphomas has yet been devised. The association between H. pylori- negative MALT lymphoma and the t(11;18)(q21;q21) translocation, resulting in an API2-MALT1 chimera gene, was reported, and is now considered one of the possible causes of and a reliable predictive marker for unresponsiveness to H. pylori-eradication treatment in patients with low-grade gastric MALT lymphoma. We report a case of H. pylori-eradication-treatment-resistant low-grade gastric MALT lymphoma that was treated successfully with radiotherapy after recognizing the API2-MALT1 chimera gene.

Clinicopathologic Study of Chromosomal Aberrations in Gastric Lymphomas of Korean Patients

BACKGROUND: The incidence and clinical correlation of MALT1 translocation and numerical aberrations in Korean gastric MALT lymphoma patients have been rarely reported. We studied the incidence and clinicopathologic relationship of these chromosomal aberrations in Korean gastric lymphomas. METHODS: Seventy-six gastric lymphomas, which consisted of 40 low grade MALT lymphoma, 4 high grade MALT lymphoma and 32 diffuse large B-cell lymphoma (DLBCL) cases, were analyzed for the detection of t(11;18) API2-MALT1, t(14;18) IgH-MALT1 and aneuploidies of chromosomes 3 or 18 using fluorescence in situ hybridization. RESULTS: The t(11;18) was demonstrated in 3 low grade MALT lymphomas (7.5%) and one DLBCL, which was associated with advanced stage, deeper invasion, and disease progression or relapse. The t(14;18) was demonstrated in none of these cases. Trisomy 3 and 18 were detected in 8 (11%) and 11 of 76 cases (12.5%) respectively, and found only in translocation-negative cases. Two of 4 high grade MALT lymphomas showed trisomy 18. All patients survived with successful second treatment after progression or relapse. CONCLUSIONS: The t(11;18) API2-MALT1 was not quite frequent in Korean low grade gastric MALT lymphomas and was associated with advanced clinical situations. Overall prognosis was good for long-term follow-up regardless of progression or relapse.

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.

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.