MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.
MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.
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MDS 显示未激活的 T 细胞中 hTERT 和选择性剪接变体的表达较高
DOI：
10.18632/oncotarget.12115
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Yang L
中科院分区：
文献类型：
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作者：
Dong W;Wu L;Sun H;Ren X;Epling-Burnette PK;Yang L
端粒不稳定和端粒酶再激活被认为在骨髓增生异常综合征（MDS）的发生发展中起重要作用。人类端粒酶逆转录酶（hTERT）的异常酶活性及其选择性剪接变体已被报道是许多癌症中端粒酶功能失调的原因。在这项研究中，我们的目的是比较hTERT和hTERT剪接变异体的表达，以及端粒长度和端粒酶活性在MDS亚组和健康对照之间的未刺激的T细胞的差异。MDS患者端粒长度明显短于对照组（n = 20，p<0.001），并使用世界卫生组织分类在MDS的所有亚型中观察到（WHO亚组与对照组：RARS，p= 0.009; RCMD，p=0.0002; RAEB 1/2，p=0.004）和国际预后评分系统（IPSS亚组：低+Int-1，p<0.001; Int-2+高，p=0.004）。然而，与对照组相比，来自MDS患者（n=20）的未刺激的T细胞具有显著更高的端粒酶活性（p=0.002）、更高的总hTERT mRNA水平（p=0.001）和hTERT α+β-剪接变体表达（p<0.001）。其他hTERT剪接变异体表达较低，在病例组和对照组之间没有显著差异。MDS患者端粒酶活性与总hTERT水平呈正相关（r=0.58，p=0.007）。该数据与我们小组先前发表的数据形成鲜明对比，这些数据显示活化后MDS T细胞中端粒酶和hTERTmRNA的减少。总之，这项研究提供了额外的洞察hTERT转录模式和活动在MDS患者的外周T细胞。需要进一步的研究来更好地了解该途径在MDS发展和进展中的作用。
Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p<0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p<0.001; Int-2+High, p=0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (p<0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.