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造血和干细胞移植中的端粒生物学。

Telomere biology in hematopoiesis and stem cell transplantation.

机构信息

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20852, USA.

出版信息

Blood Rev. 2011 Nov;25(6):261-9. doi: 10.1016/j.blre.2011.06.004. Epub 2011 Jul 20.

Abstract

Telomeres are long (TTAGGG)(n) nucleotide repeats and an associated protein complex located at the end of the chromosomes. They shorten with every cell division and, thus are markers for cellular aging, senescence, and replicative capacity. Telomere dysfunction is linked to several bone marrow disorders, including dyskeratosis congenita, aplastic anemia, myelodysplastic syndrome, and hematopoietic malignancies. Hematopoietic stem cell transplantation (HSCT) provides an opportunity in which to study telomere dynamics in a high cell proliferative environment. Rapid telomere shortening of donor cells occurs in the recipient shortly after HSCT; the degree of telomere attrition does not appear to differ by graft source. As expected, telomeres are longer in recipients of grafts with longer telomeres (e.g., cord blood). Telomere attrition may play a role in, or be a marker of, long term outcome after HSCT, but these data are limited. In this review, we discuss telomere biology in normal and abnormal hematopoiesis, including HSCT.

摘要

端粒是位于染色体末端的长(TTAGGG)(n)核苷酸重复序列和相关蛋白复合物。它们在每次细胞分裂时都会缩短,因此是细胞衰老、衰老和复制能力的标志物。端粒功能障碍与几种骨髓疾病有关,包括先天性角化不良、再生障碍性贫血、骨髓增生异常综合征和造血恶性肿瘤。造血干细胞移植(HSCT)提供了一个机会,可以在高细胞增殖环境中研究端粒动力学。HSCT 后不久,供体细胞在受体内迅速缩短端粒;端粒损耗的程度似乎与移植物来源无关。正如预期的那样,来自端粒较长(例如,脐带血)供体的移植物的端粒更长。端粒损耗可能在 HSCT 后长期结果中起作用或作为标志物,但这些数据有限。在这篇综述中,我们讨论了正常和异常造血中的端粒生物学,包括 HSCT。

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