文章：

白血病中的端粒长度特征——从端粒缩短的分子机制到针对端粒酶的免疫治疗策略

The Telomere Length Signature in Leukemias—From Molecular Mechanisms Underlying Telomere Shortening to Immunotherapeutic Options Against Telomerase

原文发布日期：10 June 2025

DOI: 10.3390/cancers17121936

类型: Article

开放获取: 是

英文摘要：

The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On the one hand, oxidative stress and mitochondrial dysfunction can accelerate telomere shortening, leading to higher susceptibility and the progression of leukemia. On the other hand, cytogenetic alterations (such as gene fusions and chromosomal abnormalities) and genomic complexity can result from checkpoint dysregulation, the induction of the DNA damage response (DDR), and defective repair signaling at telomeres. This review thoroughly outlines the ways by which telomere dysfunction can play a key role in the development and progression of four primary leukemias, including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute leukemias of myeloid or lymphoid origin, highlighting the potential prognostic value of telomere length in this field. However, telomerase, which is highly active in leukemias, can prevent the rate of telomere attrition. In line with this, leukemia cells can proliferate, suggesting telomerase as a promising therapeutic target in leukemias. For this reason, telomerase-based immunotherapy is analyzed in the fight against leukemias, leveraging the immune system to eliminate leukemia cells with uncontrolled proliferation.

摘要翻译： 

被称为端粒的核蛋白结构通过保护染色体末端来维持基因组完整性。肿瘤发生与端粒功能和稳定性的改变密切相关。本叙述性综述提供了端粒长度和端粒酶在白血病中潜在预后价值的证据。一方面，氧化应激和线粒体功能障碍可加速端粒缩短，导致更高的白血病易感性和疾病进展。另一方面，细胞遗传学改变（如基因融合和染色体异常）及基因组复杂性可能源于检查点失调、DNA损伤反应（DDR）的诱导以及端粒修复信号传导缺陷。本综述系统阐述了端粒功能障碍在四种主要白血病（包括慢性淋巴细胞白血病、慢性粒细胞白血病、髓系或淋巴系急性白血病）发生发展中的关键作用机制，并重点强调了端粒长度在该领域的潜在预后价值。然而，在白血病中高度活跃的端粒酶能够延缓端粒损耗速率。与此相应，白血病细胞得以持续增殖，这提示端粒酶可作为白血病治疗的重要靶点。基于此，本文分析了基于端粒酶的免疫疗法在对抗白血病中的应用前景，该疗法通过调动免疫系统来清除具有失控增殖特性的白血病细胞。

原文链接：

The Telomere Length Signature in Leukemias—From Molecular Mechanisms Underlying Telomere Shortening to Immunotherapeutic Options Against Telomerase