Counter C M, Gupta J, Harley C B, Leber B, Bacchetti S
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Blood. 1995 May 1;85(9):2315-20.
Telomeres are essential for function and stability of eukaryotic chromosomes. In the absence of telomerase, the enzyme that synthesizes telomeric DNA, telomeres shorten with cell division, a process thought to contribute to cell senescence and the proliferative crisis of transformed cells. We reported telomere stabilization concomitant with detection of telomerase activity in cells immortalized in vitro and in ovarian carcinoma cells, and suggested that telomerase is essential for unlimited cell proliferation. We have now examined the temporal pattern of telomerase expression in selected hematologic malignancies. We found that, unlike other somatic tissues, peripheral, cord blood, and bone marrow leukocytes from normal donors expressed low levels of telomerase activity. In leukocytes from chronic lymphocytic leukemia (CLL) patients, activity was lower than in controls in early disease, and comparable with controls in late disease. Relative to bone marrow, telomerase activity was enhanced in myelodysplastic syndrome (MDS) and more significantly so in acute myeloid leukemia (AML). Regardless of telomerase levels, telomeres shortened with progression of the diseases. Our results suggest that early CLL and MDS cells lack an efficient mechanism of telomere maintenance and that telomerase is activated late in the progression of these cancers, presumably when critical telomere loss generates selective pressure for cell immortality.
端粒对于真核染色体的功能和稳定性至关重要。在缺乏合成端粒DNA的酶——端粒酶的情况下，端粒会随着细胞分裂而缩短，这一过程被认为与细胞衰老及转化细胞的增殖危机有关。我们报道了在体外永生化细胞和卵巢癌细胞中检测到端粒酶活性时伴随的端粒稳定现象，并提出端粒酶对于细胞的无限增殖至关重要。我们现在研究了特定血液系统恶性肿瘤中端粒酶表达的时间模式。我们发现，与其他体细胞组织不同，正常供体的外周血、脐带血和骨髓白细胞表达的端粒酶活性水平较低。在慢性淋巴细胞白血病（CLL）患者的白细胞中，疾病早期活性低于对照组，疾病晚期与对照组相当。相对于骨髓，骨髓增生异常综合征（MDS）中端粒酶活性增强，在急性髓系白血病（AML）中更为显著。无论端粒酶水平如何，端粒都会随着疾病进展而缩短。我们的结果表明，早期CLL和MDS细胞缺乏有效的端粒维持机制，并且端粒酶在这些癌症进展后期被激活，推测是在关键端粒丢失产生细胞永生的选择性压力时。
