Chromosome translocation junction genes on lympho-hematopoietic cell proliferation and differentiation

染色体易位连接基因对淋巴造血细胞增殖和分化的影响

基本信息

批准号：
11470215
负责人：
SETO Masao
金额：
$ 9.34万
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：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470215/
关键词：
MALT lymphoma MALT1 API2 API2-MALT1 Chromosome translocation lymphoma Diffuse large B cell lymphoma TCBA1 びまん性リンパ腫 B細胞分化アポトーシス

项目摘要

We have reported a novel gene MALT1 at chromosome 18q21 that is involved in mucosa-associated lymphoid tissue (MALT) lymphoma t(11;18)(q21;q21). This translocation results in fusion between API2 at 11q21 and MALT1 at 18q21, producing API2-MALT1 chimeric products. We are now trying to produce monoclonal antibodies against API2 and MALT1 products so that we can examine MALT lymphoma cases with immunohistochemial method.We have studied diffuse large B cell lymphoma(DLBCL) that was known to contain several subtypes although consensus for subtype classifications is difficult to obtain among various hematopathologists. We have examined BCL1, BCL2, BCL6 gene rearrangement as well as immunostaining. We found that cell surface markers could serve as markers depicting clinically significant subtypes. Indeed, CD5+ DLBCL was found to consist of a group with poor prognosis which is as worse as mantle cell lymphoma.Translocation junction genes that are involved in T-cell lymphoma are poorly understood. Based on the reports that T-cell lymphoma had frequent chromosome aberration at 6q21, we attempted to isolate the responsible genes. We identified a novel TCBA1 gene that is altered in T-cell lymphoblastoid lymphoma cell line HT-1 and adult T-cell leukemia/lymphoma cell line ATM-1. The role of TCBA1 for lymphomageneis is now under investigation.

我们报道了染色体 18q21 上的一个新基因 MALT1，该基因参与粘膜相关淋巴组织 (MALT) 淋巴瘤 t(11;18)(q21;q21)。这种易位导致 11q21 处的 API2 和 18q21 处的 MALT1 融合，产生 API2-MALT1 嵌合产物。我们现在正在尝试生产针对 API2 和 MALT1 产品的单克隆抗体，以便我们可以用免疫组织化学方法检查 MALT 淋巴瘤病例。我们已经研究了弥漫性大 B 细胞淋巴瘤 (DLBCL)，已知它包含多种亚型，尽管亚型分类很难达成共识从不同的血液病理学家中获取。我们检查了 BCL1、BCL2、BCL6 基因重排以及免疫染色。我们发现细胞表面标记物可以作为描述临床重要亚型的标记物。事实上，CD5+ DLBCL 被发现是由一组预后不良组成的，其与套细胞淋巴瘤一样糟糕。T 细胞淋巴瘤中涉及的易位连接基因知之甚少。根据 T 细胞淋巴瘤 6q21 频繁出现染色体畸变的报道，我们尝试分离出相关基因。我们鉴定出一种新的 TCBA1 基因，该基因在 T 细胞淋巴母细胞淋巴瘤细胞系 HT-1 和成人 T 细胞白血病/淋巴瘤细胞系 ATM-1 中发生改变。 TCBA1 在淋巴瘤发生中的作用目前正在研究中。