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，是其稳定维护的染色体的必要成分。它们显示出高度动态的变化，这是由于细胞生长和端粒伸长症而由于端粒活性引起的端粒伸长率之间的平衡而产生的。我们测量了正常外周血细胞中的端粒长度，发现它们随着捐助者的年龄增加而缩短。在白血病细胞中，与正常细胞相比，端粒长度始终缩短。我们开发了一种新型的定量拉伸PCR分析，以促进端粒酶活性。端粒酶在大多数正常血细胞中都是负面的。相比之下，它在恶性肿瘤的晚期阶段被高度激活，例如CML的Blastic危机和AML的复发病例。提出了端粒危机模型来解释具有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。”

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。”

Ikeda-Nishizawa, Y., Yazaki, Y., Hirai, H.and Ishikawa, F.: "Spatial progression of DNA strand breads in apoptotic HL-60 cells." Bioimages. 4. 63-72 (1996)

Ikeda-Nishizawa, Y.、Yazaki, Y.、Hirai, H. 和 Ishikawa, F.：“凋亡 HL-60 细胞中 DNA 链面包的空间进展。”