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端粒结合蛋白的异常mRNA表达水平可作为骨髓增生异常综合征的生物标志物:一项病例对照研究。

Abnormal mRNA Expression Levels of Telomere-Binding Proteins Represent Biomarkers in Myelodysplastic Syndromes: A Case-Control Study.

作者信息

Liu Baoshan, Yan Rongdi, Zhang Jie, Wang Bin, Sun Hu, Cui Xing

机构信息

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hematology, Jinan, China.

出版信息

Turk J Haematol. 2017 Aug 2;34(3):200-206. doi: 10.4274/tjh.2016.0364. Epub 2017 Apr 13.

Abstract

OBJECTIVE

As evidence was shown that abnormal shortening of telomeres begins to accumulate in myelodysplastic syndrome (MDS) patients, this study was conducted to determine the relationship between the mRNA expression levels of telomere-binding proteins (TRF1/TRF2/TIN2/TPP1/POT1/RAP1) and the risk level in MDS.

MATERIALS AND METHODS

There were 40 patients with MDS and 40 normal controls in this study. Methods including telomere content assays and quantitative reverse transcription-polymerase chain reaction were used to examine the mRNA levels of TRF1/TRF2/TIN2/TPP1/POT1/RAP1 in patients with MDS.

RESULTS

Compared to the normal group used as a control, the mRNA expression levels of RAP1/POT1/TPP1 of the patients with MDS were decreased, whereas their levels of TRF1/TRF2 and TIN2 were increased. A positive correlation was found between the TRF1, TRF2, and TIN2 mRNA expression levels and the risk level of the International Prognostic Scoring System (IPSS) and the World Health Organization Prognostic Scoring System (WPSS) criteria; however, a negative correlation was found between RAP1/POT1/TPP1 mRNA expression levels and the risk levels of IPSS and WPSS criteria.

CONCLUSION

Because the reduction of TRF1/TRF2/TIN2 mRNA expression and the increase of RAP1/POT1/TPP1 mRNA expression are closely related to the risk levels of the IPSS and WPSS criteria in MDS, it is thought that these telomere-binding proteins could lead to abnormal telomere length and function, which cause chromosomal abnormalities in MDS. With this evidence, we suggest that those proteins' mRNA expressions could be used as biomarkers for the assessment of the risk degree of MDS patients.

摘要

目的

有证据表明骨髓增生异常综合征(MDS)患者端粒开始异常缩短,本研究旨在确定端粒结合蛋白(TRF1/TRF2/TIN2/TPP1/POT1/RAP1)的mRNA表达水平与MDS风险水平之间的关系。

材料与方法

本研究纳入40例MDS患者和40例正常对照。采用端粒含量测定和定量逆转录-聚合酶链反应等方法检测MDS患者TRF1/TRF2/TIN2/TPP1/POT1/RAP1的mRNA水平。

结果

与正常对照组相比,MDS患者RAP1/POT1/TPP1的mRNA表达水平降低,而TRF1/TRF2和TIN2的水平升高。发现TRF1、TRF2和TIN2的mRNA表达水平与国际预后评分系统(IPSS)和世界卫生组织预后评分系统(WPSS)标准的风险水平呈正相关;然而,RAP1/POT1/TPP1的mRNA表达水平与IPSS和WPSS标准的风险水平呈负相关。

结论

由于TRF1/TRF2/TIN2 mRNA表达降低和RAP1/POT1/TPP1 mRNA表达增加与MDS中IPSS和WPSS标准的风险水平密切相关,认为这些端粒结合蛋白可能导致端粒长度和功能异常,进而引起MDS中的染色体异常。基于此证据,我们建议这些蛋白的mRNA表达可作为评估MDS患者风险程度的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/966c/5544038/949667bb3c8e/TJH-34-200-g4.jpg

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