Deville Laure, Hillion Josette, Lanotte Michel, Rousselot Philippe, Ségal-Bendirdjian Evelyne
INSERM U685, Hôpital Saint-Louis, 75010 Paris, France.
Curr Pharm Biotechnol. 2006 Jun;7(3):171-83. doi: 10.2174/138920106777549768.
Telomeres are specialized structures at the end of human chromosomes. Telomere length decreases with each cell division, thus, reflecting the mitotic history of somatic cells. Telomerase, the ribonucleoprotein enzyme which maintains telomeres of eukaryotic chromosomes, is up-regulated in the vast majority of human neoplasia but not in normal somatic tissues. In contrast to other somatic cells, normal primitive human hematopoietic cells and some peripheral blood cells expressed low levels of telomerase activity. This activity is thought to play an important role in self-renewal of hematopoietic stem cells. In malignant disorders, telomere lengths are generally shortened and telomerase expression and activity enhanced with high differences in the levels. Although it is necessary to be cautious in interpreting these data, there are indications that telomere length and telomerase expression and activity can serve as a molecular marker of the clinical progression and prognosis of most leukemias. Approaches that directly target telomerase, telomeres or telomerase regulatory mechanisms have been developed. Some of these anti-telomerase strategies in combination with conventional drugs proved to be promising in some types of leukemias.
端粒是人类染色体末端的特殊结构。端粒长度随细胞每次分裂而缩短，因此反映了体细胞的有丝分裂历史。端粒酶是一种维持真核染色体端粒的核糖核蛋白酶，在绝大多数人类肿瘤中上调，但在正常体细胞组织中则不然。与其他体细胞不同，正常原始人类造血细胞和一些外周血细胞表达低水平的端粒酶活性。这种活性被认为在造血干细胞的自我更新中起重要作用。在恶性疾病中，端粒长度通常缩短，端粒酶表达和活性增强，且水平差异很大。尽管在解释这些数据时需要谨慎，但有迹象表明端粒长度、端粒酶表达和活性可作为大多数白血病临床进展和预后的分子标志物。已经开发出直接靶向端粒酶、端粒或端粒酶调节机制的方法。其中一些抗端粒酶策略与传统药物联合使用在某些类型的白血病中已被证明很有前景。
