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

端粒是染色体的末端，是维持染色体稳定的重要组成部分，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的平衡，呈现出高度的动态变化。我们测量了正常外周血细胞的端粒长度，发现端粒长度随着捐赠者年龄的增加而缩短。在白血病细胞中，与正常细胞相比，端粒长度总是缩短的。我们建立了一种新的定量拉伸PCR方法来检测端粒酶活性。端粒酶在大多数正常血细胞中均为阴性。相反，在晚期恶性肿瘤中，如CML的急变期和AML的复发期，端粒高度激活。

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.