Norrback K F, Roos G
Department of Pathology, Umeå University, Sweden.
Eur J Cancer. 1997 Apr;33(5):774-80. doi: 10.1016/S0959-8049(97)00059-2.
The normal haematopoietic system harbours telomerase-competent cells with a capacity to upregulate the activity to notable levels in a telomere length-independent manner. Strong telomerase activity is found in progenitor stem cells and activated lymphocytes in vitro as well as in vivo, indicating that cells with high growth requirements can readily upregulate telomerase. Despite detection of telomerase activity, a gradual telomere erosion occurs in stem cells and lymphocytes, with significantly shortened telomeres at higher ages, a phenomenon that might be of importance for developing immunosenescence and exhausted haematopoiesis. In malignant haematopoietic disorders telomerase activity is a general finding with large differences in activity levels. The strongest telomerase expression has been shown in acute leukaemias and non-Hodgkin's lymphomas, especially high grade cases. There are indications that the level of activity might parallel tumour progression and be of prognostic relevance, but studies of larger patient materials are needed. An association between the cell cycle and telomerase activity exists, especially for normal haematopoietic cells, and induction of a differentiation programme in immortalised cell lines downregulates telomerase activity. The expression of telomerase activity seems to be regulated at different levels, since for immature bone marrow cells the level of activity seemed to parallel better the phenotype than the proliferation state. The frequent expression of telomerase in leukaemias and lymphomas makes these disorders interesting targets for future anti-telomerase therapy.
正常造血系统中存在具有端粒酶活性的细胞，这些细胞能够以与端粒长度无关的方式将活性上调至显著水平。在祖干细胞和活化淋巴细胞中，无论在体外还是体内均能检测到较强的端粒酶活性，这表明具有高生长需求的细胞能够轻易上调端粒酶活性。尽管检测到端粒酶活性，但干细胞和淋巴细胞中仍会发生端粒逐渐缩短的现象，在老年时端粒会显著缩短，这一现象可能对免疫衰老和造血功能衰竭的发生具有重要意义。在恶性造血疾病中，端粒酶活性是普遍存在的现象，但其活性水平差异很大。在急性白血病和非霍奇金淋巴瘤中，尤其是高级别病例中，端粒酶表达最强。有迹象表明，活性水平可能与肿瘤进展平行且具有预后相关性，但需要对更多患者样本进行研究。细胞周期与端粒酶活性之间存在关联，特别是对于正常造血细胞而言，在永生化细胞系中诱导分化程序会下调端粒酶活性。端粒酶活性的表达似乎在不同水平受到调控，因为对于未成熟骨髓细胞，活性水平似乎与表型的相关性优于与增殖状态的相关性。白血病和淋巴瘤中端粒酶的频繁表达使得这些疾病成为未来抗端粒酶治疗的有趣靶点。
