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Analysis of immunoglobulin, T cell receptor and cytokine genes in hematologic neoplasms

血液肿瘤中免疫球蛋白、T细胞受体和细胞因子基因分析

基本信息

批准号：
61480260
负责人：
TAKATSUKI Kiyoshi
金额：
$ 4.48万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480260/
关键词：
Leukemia Non-Hodgkin's lymphoma Adult T cell leukemia Tmmunoglobulin gene T cell receptor gene HTLV-I HTLV-I リンパ腫 T細胞受容体 -CD3複合体 HTLV-1 発癌機構細胞分化増殖因子

项目摘要

Rearrangements of immunoglobulin (Ig) or T cell receptor (TCR) chain gene were observed in all of lymph node cells from phenotypically undetermined cell lymphoma, suggesting that demonstration of these gene rearrangements is a powerful tool to determine cell lineage and clonality. TCR chain gene rearrangement was frequently found in both T cell and immature B cell neoplasms and was not observed in mature B cell neoplasms. Furthermore, rearrangement of TCR chain gene was also found in immature B cell leukemias associated with TCR chain gene rearrangement. These results indicate that an analysis of Ig and TCR gene provides a potential tool to identify the normal stages of lymphocyte differentiation. The density of TCR and CD3 antigens on adult T cell leukemia (ATL) cells are low, indicating that interactions of atnigents to CD3-TCR complex induce their modulation. No significant homologies were noted among the deduced amino acid sequences of variable lesions of TCR chain, and the plofiles of rearrangement patterns of TCR and chain gene in ATL cells were heterogenous. However, there were apparent associations between a defect of expression of CD3-TCR complex and identical genotypes of fresh and cultured cells, suggesting that the defect of expression of CD3-TCR complex may play a key role for development of ATL. On the other hand, a significant proliferation by IL-1, which were inhibited by anti-IL-1 antibody, was observed in cells from a patient with myeloid leukemia. Culture supernatants of these leukemic cells contained IL-1 activity and northern blot analysis detected intracellular IL-1 mRNA, indicating that autocrine secretion of IL-1 was involved in proliferation of some myeloid leukemic cells. Thus, an analysis of Ig, TCR and cytokine genes is a powerful tool to classify and characterize hematologic neoplasms.

免疫球蛋白（IG）或T细胞受体（TCR）链基因重排在所有表型未定细胞淋巴瘤的淋巴结细胞中均被观察到，提示这些基因重排的证明是确定细胞谱系和克隆性的有力工具。TCR链基因重排在T细胞和未成熟B细胞肿瘤中经常发现，而在成熟B细胞肿瘤中未观察到。此外，在未成熟B细胞白血病中也发现了TCR链基因重排。这些结果表明，IG和TCR基因的分析提供了一个潜在的工具，以确定淋巴细胞分化的正常阶段。成人T细胞白血病（ATL）细胞表面TCR和CD 3抗原密度较低，表明补体与CD 3-TCR复合物的相互作用诱导了它们的调节。在ATL细胞中，TCR链可变区的氨基酸序列之间没有明显的同源性，TCR和链基因重排模式的谱图是异质性的。然而，CD 3-TCR复合物的表达缺陷与新鲜细胞和培养细胞的相同基因型之间存在明显的相关性，表明CD 3-TCR复合物的表达缺陷可能在ATL的发生中起关键作用。另一方面，在来自骨髓性白血病患者的细胞中观察到IL-1的显著增殖，其被抗IL-1抗体抑制。这些白血病细胞的培养上清含有IL-1活性，北方印迹分析检测到细胞内IL-1 mRNA，表明IL-1的自分泌参与了某些髓系白血病细胞的增殖。因此，分析IG、TCR和细胞因子基因是对血液肿瘤进行分类和表征的有力工具。