Cancer Bio-Immunotherapy Unit, Department of Medical Oncology, CRO-IRCCS, National Cancer Institute, Aviano, Italy.
Med Res Rev. 2012 Mar;32(2):233-53. doi: 10.1002/med.20211. Epub 2010 Jun 14.
Telomerase is a ribonucleoprotein complex critically involved in extending and maintaining telomeres. Unlike the majority of somatic cells, in which hTERT and telomerase activity are generally silent, normal lymphocytes show transient physiological hTERT expression and telomerase activity according to their differentiation/activation status. During lymphomagenesis, induction of persistent telomerase expression and activity may occur before or after telomere shortening, as a consequence of the different mechanisms through which transforming factors/agents may activate telomerase. Available data indicate that the timing of telomerase activation may allow the distinction of two different lymphomagenetic models: (i) an early activation of telomerase via exogenous regulators of hTERT, along with an increased lymphocyte growth and a subsequent selection of cells with increased transforming potential may characterize several virus-related lymphoid malignancies; (ii) a progressive shortening of telomeres, leading to genetic instability which favors a subsequent activation of telomerase via endogenous regulators may occur in most virus-unrelated lymphoid tumors. These models may have clinically relevant implications, particularly for the tailoring of therapeutic strategies targeting telomerase.
端粒酶是一种核糖核蛋白复合物，在延长和维持端粒方面起着关键作用。与大多数体细胞不同，在这些体细胞中，hTERT 和端粒酶活性通常处于沉默状态，正常淋巴细胞根据其分化/激活状态表现出短暂的生理性 hTERT 表达和端粒酶活性。在淋巴瘤发生过程中，端粒酶表达和活性的持续诱导可能发生在端粒缩短之前或之后，这是转化因子/剂通过不同的机制激活端粒酶的结果。现有数据表明，端粒酶激活的时间可能允许区分两种不同的淋巴瘤发生模型：（i）通过 hTERT 的外源调节剂早期激活端粒酶，同时增加淋巴细胞的生长，并随后选择具有增加转化潜能的细胞，这可能是几种与病毒相关的淋巴恶性肿瘤的特征；（ii）端粒的逐渐缩短，导致遗传不稳定性，随后通过内源性调节剂激活端粒酶，这可能发生在大多数与病毒无关的淋巴肿瘤中。这些模型可能具有临床相关意义，特别是在制定针对端粒酶的治疗策略时。
