API2-MALT1 translocation and tumorgenesis in gastric MALT lymphoma

API2-MALT1 易位与胃 MALT 淋巴瘤的肿瘤发生

• 批准号: 14570437
• 负责人: SUGIYAMA Toshiro
• 金额: $ 2.37万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570437/
• 关键词: H.pylon; Gastric MALT lymphoma; API2-MALT1 chimeric transcript; NF-kB activation; NF-κB; アポトーシス

Total gastrectomy was an established conventional treatment against gastric MALT lymphoma. As the 60-80% of gastric MALT lymphoma regress by an eradication treatment of H.pylon and the remaining 20-40% does not, the predictive factor to eradication treatment should be clinically identified. The translocation between API2 gene in Ch11 and MALT1 gene in Ch18 was observed in a part of gastric MALT lymphoma and the high sensitive detection method of the chimeric transcript was established By using this system, the presence of API2-MALT1 chimeric transcript was an important predictive factor to resist for eradication treatment. These results suggest us that the presence of API2-MALT1 chimeric transcript might have a causal linkage to occurrence of eradication-resistant gastric MALT lymphoma. The transfection of API2-MALT1 chimeric cDNA into COS7 cells have induced an accumulation of the chimeric protein within the cytoplasm and demonstrated the delayed degradation of the protein. The accumulation of the chimeric protein within the cytoplasm resulted in an activation of NF-kB in the nucleus. Therefore, the presence of API2-MALT1 chimenc transcript might have a causal linkage to tumorgenesis via NF-kB activation in eradication-resistant gastric MALT lymphoma.

全胃切除术是治疗胃MALT淋巴瘤的传统方法。由于60-80%的胃MALT淋巴瘤通过根除幽门螺杆菌治疗而消退，而其余20-40%则没有，因此根除治疗的预测因素应在临床上确定。在部分胃MALT淋巴瘤中观察到Ch 11的API 2基因和Ch 18的MALT 1基因的易位，并建立了高灵敏度的嵌合体转录本检测方法。利用该系统，API 2-MALT 1嵌合体转录本的存在是抵抗根除治疗的重要预测因子。这些结果提示，API 2-MALT 1嵌合体转录本的存在可能与胃MALT淋巴瘤的发生有因果关系。将API 2-MALT 1嵌合cDNA转染入COS 7细胞中诱导了嵌合蛋白在细胞质内的积累，并证明了蛋白的延迟降解。嵌合蛋白在细胞质内的积累导致核中NF-κ B的活化。因此，API 2-MALT 1嵌合体转录本的存在可能与根除抗性胃MALT淋巴瘤中通过NF-κ B活化的肿瘤发生存在因果关系。

项目成果

Kaminishi M, Sugiyama T et al.: "Endoscopic classification of chronic gastritis based on a pilot study by the research society for gastritis"Digestive Endoscopy. 14. 138-151 (2002)

Kaminishi M、Sugiyama T 等人：“基于胃炎研究会试点研究的慢性胃炎内镜分类”消化内镜检查。

Sugiyama T, Asaka M: "H.pylori eradication for intractable gastric ulcer"Aliment Pharmacol Ther. 18. 543-544 (2003)

Sugiyama T、Asaka M：“根除幽门螺杆菌治疗顽固性胃溃疡”Aliment Pharmacol Ther。

Sugiyama T, et al.: "H.Pylori eradication for intractable gastric ulcer"Aliment Pharmacol Ther. 18. 543-544 (2003)

Sugiyama T 等：“顽固性胃溃疡的幽门螺杆菌根除”Aliment Pharmacol Ther。

Marchildon PA, Sugiyama T, Fukuda Y.Asaka M, Shimoyama T, Graham, DY: "Evaluation of the effects of strain-specific antigen variation on the accuracy of serologic diagnosis of Helicobacter pylori lnfection"J Clin Microbiol. 41. 1480-1485 (2003)

Marchildon PA、Sugiyama T、Fukuda Y.Asaka M、Shimoyama T、Graham、DY：“评估菌株特异性抗原变异对幽门螺杆菌感染血清学诊断准确性的影响”J Clin Microbiol。

Sugiyama T et al.: "Sensitivity biopsy site in evaluating regression of gastric atrophy after Helicobacter pylori eradication treatment"Aliment Pharmacol Ther. 16. 187-190 (2002)

Sugiyama T 等人：“敏感性活检部位评估幽门螺杆菌根除治疗后胃萎缩消退”Aliment Pharmacol Ther。