Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
J Hematol Oncol. 2013 Apr 2;6:26. doi: 10.1186/1756-8722-6-26.
The predominant mechanism by which human tumors maintain telomere length is via telomerase. In ~10% of tumor samples, however, telomere length is conserved, despite no detectable telomerase activity, in part through activation of the alternative lengthening of telomeres (ALT) pathway.
We studied the circular extra-chromosomal telomeric repeat (ECTR), an ALT hallmark, and telomerase activity in 24 chronic myeloid leukemia (CML) patients in chronic phase (CP).
We identified the presence of ECTR in primary leukemia cells from some of these samples, which indicates the possible involvement of an ALT mechanism. Moreover, we found that some samples exhibited both circular ECTR and telomerase activities, suggesting that both mechanisms can contribute to the onset of CML.
We propose that ALT or the combined activities of ALT and telomerase might be required for the early stages of leukemogenesis. These findings shed new light into the oncogenic pathways responsible for the maintenance of telomere length in leukemia, which will ultimately determine the effectiveness of anti-telomerase-based treatment protocols.
人类肿瘤维持端粒长度的主要机制是通过端粒酶。然而，在约 10%的肿瘤样本中，尽管没有检测到端粒酶活性，但端粒长度仍然得到维持，部分原因是通过激活端粒的替代性延长（ALT）途径。
我们研究了 24 例慢性髓性白血病（CML）慢性期（CP）患者的环状染色体外端粒重复（ECTR），这是 ALT 的一个标志，以及端粒酶活性。
我们在这些样本中的一些原发性白血病细胞中发现了 ECTR 的存在，这表明可能涉及 ALT 机制。此外，我们发现一些样本同时表现出环状 ECTR 和端粒酶活性，表明这两种机制都可能导致 CML 的发生。
我们提出 ALT 或 ALT 和端粒酶的联合活性可能是白血病发生的早期所必需的。这些发现为负责白血病中端粒长度维持的致癌途径提供了新的线索，这最终将决定基于抗端粒酶的治疗方案的有效性。
