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Roles of translocation junction genes for proliferation and differentiation of hemotolymphoid cell

易位连接基因对血淋巴细胞增殖和分化的作用

基本信息

批准号：
14370312
负责人：
SETO Masao
金额：
$ 8.9万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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-14370312/
关键词：
Lymphoma T-cell lymphoma MALT Lymphoma API2-MALT1 API2 MALT1 Tissue-FISH 染色体転座ゲノム転座関連遺伝子 T細胞リンパ腫 T NKリンパ腫

项目摘要

The aim of the study is to identify genes that are involved in proliferation, differentiation and apoptosis for hematolymphoid cells and establish molecular markers useful for diagnosis and therapy. We have analyzed T-cell lymphoma breakpoint of chromosome 6q21 and identified TCBA1 (T-cell breakpoint cluster target 1). Its function on lymphomagenesis and cell differentiation remains to be explored. Mucosa-associated lymphoid tissue (MALT) lymphoma arises with chronic inflammation caused by H.pylori (gastric MALT lymphoma) or autoimmune diseases. Therefore, tumor cells are mixed with variable number of inflammatory cells.In an attempt to analyze heterogeneity of MALT lymphoma, we measured API2-MALT1 chimeric mRNA copy number by REAL-Time PCR and tumor cell ratio by IgVH genomic sequence. As a result, API2-MALT1 copy number per tumor cell was found to vary as much as 100 times among the patients. This indicates that the heterogeneity of MALT lymphoma may be reflected by the amount of tumor cell and also by API2-MLAT1 chimeric mRNA copy number. MALT lymphoma without API2-MALT1 chimeric mRNA is also an important disease category to be explored. We are applying Tissue FISH method to this problem. Function of the concogenic gene is an important issue. Retroviral vector is being used and in combination with stem cell transplantation, in vivo function of API2-MALT1 is being studied.

本研究的目的是找出与血淋巴细胞增殖、分化和凋亡相关的基因，并建立对诊断和治疗有用的分子标记。我们已经分析了染色体6q21的T细胞淋巴瘤断裂点，并确定了TCBA1(T细胞断裂点簇靶点1)。其在淋巴生成和细胞分化中的作用还有待进一步研究。粘膜相关淋巴组织(MALT)淋巴瘤是由幽门螺杆菌(胃MALT淋巴瘤)或自身免疫性疾病引起的慢性炎症引起的。为了分析MALT淋巴瘤的异质性，我们用实时定量聚合酶链式反应检测API2-MALT1嵌合mRNA拷贝数，用IgVH基因组测序检测肿瘤细胞比率。结果发现，每个肿瘤细胞的API2-MALT1拷贝数在不同患者之间差异高达100倍。提示MALT淋巴瘤的异质性可能通过肿瘤细胞的数量和API2-MLAT1嵌合的mRNA拷贝数来反映。缺乏API2-MALT1嵌合mRNA的MALT淋巴瘤也是一个有待探索的重要疾病类别。我们正在应用组织鱼方法来解决这个问题。癌基因的功能是一个重要的问题。正在使用逆转录病毒载体，并结合干细胞移植，正在研究API2-MALT1的体内功能。