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.

该研究的目的是鉴定参与血淋巴细胞增殖、分化和凋亡的基因，并建立可用于诊断和治疗的分子标记。我们分析了染色体 6q21 的 T 细胞淋巴瘤断点并确定了 TCBA1（T 细胞断点簇目标 1）。其对淋巴瘤发生和细胞分化的功能仍有待探索。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。因此，肿瘤细胞与不同数量的炎症细胞混合。为了分析MALT淋巴瘤的异质性，我们通过实时PCR测量了API2-MALT1嵌合mRNA拷贝数，并通过IgVH基因组序列测量了肿瘤细胞比例。结果发现，每个肿瘤细胞的 API2-MALT1 拷贝数在患者之间存在高达 100 倍的差异。这表明MALT淋巴瘤的异质性可能通过肿瘤细胞的数量来反映，也可以通过API2-MLAT1嵌合mRNA的拷贝数来反映。没有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 FISH 方法来解决这个问题。同源基因的功能是一个重要问题。正在使用逆转录病毒载体并与干细胞移植相结合，研究API2-MALT1的体内功能。