Xu D, Zheng C, Bergenbrant S, Holm G, Björkholm M, Yi Q, Gruber A
Department of Medicine, Division of Hematology, Karolinska Hospital, SE-171 76, Stockholm, Sweden.
Br J Cancer. 2001 Mar 2;84(5):621-5. doi: 10.1054/bjoc.2000.1655.
Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM.
端粒酶的激活对于体外细胞永生化和肿瘤发生至关重要。在本研究中,我们调查了端粒酶激活及其在浆细胞异常增殖疾病中的意义,这些疾病包括意义未明的单克隆丙种球蛋白病(MGUS)、多发性骨髓瘤(MM)和浆细胞白血病(PCL)。所有5例MGUS患者的浆细胞中端粒酶活性水平均正常。在21/27例MM患者和4/4例PCL患者的样本中发现端粒酶活性升高。此外,4种骨髓瘤细胞系均表达高水平的端粒酶活性。端粒酶逆转录酶(hTERT)和端粒酶RNA模板(hTER)的表达与MM/PCL中端粒酶活性水平呈正相关。在MM/PCL中,端锚聚合酶表达上调,同时伴有hTERT的诱导和端粒酶的激活。本研究结果表明,MGUS细胞可能不会永生化,端粒酶的激活在MGUS向MM的恶性转化中起作用。