Department of Haematology,School of Medicine, Cardiff University, Cardiff, UK.
Br J Haematol. 2012 Mar;156(5):573-87. doi: 10.1111/j.1365-2141.2011.09022.x. Epub 2012 Jan 11.
Observations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large-scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies extreme telomere shortening, telomere dysfunction and fusion have all been documented and correlate with the emergence of increased genomic complexity. Telomeres may therefore represent both a clinically useful prognostic tool and a potential target for therapeutic intervention.
在人类肿瘤以及小鼠模型中的观察结果表明，端粒功能障碍可能是许多实体瘤类型中驱动基因组不稳定性和疾病进展的关键事件。在这种情况下，端粒缩短最终会导致端粒功能障碍、融合和基因组不稳定性，从而产生这些肿瘤的特征性大规模重排。现在越来越明显的是，这一模式也可能适用于血液系统恶性肿瘤；事实上，这些疾病为任何恶性肿瘤中端粒功能障碍提供了一些最有说服力的证据。在几种恶性肿瘤中，端粒长度已被证明可提供具有临床意义的预后信息，表明端粒功能障碍与疾病进展有关。在这些恶性肿瘤中，已经记录到极端的端粒缩短、端粒功能障碍和融合，并且都与基因组复杂性的增加相关。因此，端粒可能既代表一种具有临床意义的预后工具，也代表一种潜在的治疗干预靶点。
