ヒトゲノム反復配列の不安定性にもとづく疾患の診断技術の開発

基于人类基因组重复序列不稳定性的疾病诊断技术开发

• 批准号: 07557043
• 负责人: ISHIKAWA Fuyuki
• 金额: $ 7.81万
• 依托单位: TOKYO INSTITUTE OF TECHNOLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557043/
• 关键词: telomere; telomerase; stretch PCR assay; leukemia; 反復配列; PCR

Telomeres, the ends of chromosomes, are essential components of chromosomes for their stable maintenance.They show a highly dynamic changes, resulted from an equilibrium between the telomere shortening due to cell growth and the telomere elongation due to the telomerase activity. We measured the telomere lengths in normal peripheral blood cells and found that they are shortened as the ages of the donors increased. In leukemic cells, the telomere lengths were invariably shortened compared to those of the normal cells.We developed a novel quantitative stretch PCR assay for the neasurement of the telomerase activity. Telomerase was negarive in most of the normal blood cells. In contrast, it was highly activated in advanced stages of malignancy, such as blastic crisis of CML and relapsed casesof AML.The telomere crisis model was proposed to explain these characteristic features with malignant cells.

端粒是染色体的末端，是染色体稳定维持的重要组成部分。它们表现出高度动态的变化，是细胞生长引起的端粒缩短和端粒酶活性引起的端粒伸长之间平衡的结果。我们测量了正常外周血细胞的端粒长度，发现它们随着捐献者年龄的增加而缩短。在白血病细胞中，与正常细胞相比，端粒长度总是缩短。我们开发了一种新颖的定量拉伸 PCR 测定法来测量端粒酶活性。大多数正常血细胞的端粒酶呈阴性。相反，它在恶性肿瘤的晚期阶段高度激活，例如CML的急变期和AML的复发病例。端粒危机模型被提出来解释恶性细胞的这些特征。

项目成果

Ishikawa, F.: "A review article : Telomere crisis in leukemia" Intl.J.Hematol.65. 355-364 (1997)

Ishikawa, F.：“综述文章：白血病中的端粒危机”Intl.J.Hematol.65。

Kajita, Y.et al.: "Bioluminescent detection of RNA with sequence-specificity using RNA binding protein-luciferase fusion protein." J.Biotechnol.43. 63-70 (1995)

Kajita, Y. 等人：“使用 RNA 结合蛋白-荧光素酶融合蛋白对具有序列特异性的 RNA 进行生物发光检测。”

Nakayama,J.: "TLP1:A gene encoding a protein component of mammalian telomerase is a novel member of WD-repeats family." Cell,in press. (1997)

Nakayama, J.：“TLP1：编码哺乳动物端粒酶蛋白质成分的基因是 WD 重复序列家族的新成员。”

Ikeda-Nishizawa, Y.et al.: "Spatial progression of DNA strand breaks in apoptotic HL-60 cells." Bioimages. 4. 63-72 (1996)

Ikeda-Nishizawa, Y.et al.：“凋亡 HL-60 细胞中 DNA 链断裂的空间进展。”

Ishikawa, F.: "A review article:Telomere crisis in leukemia." Intl.J.Hematol.65. 355-364 (1997)

Ishikawa, F.：“一篇评论文章：白血病的端粒危机。”