Telomere length and telomerase reverse transcriptase gene polymorphism as potential markers of complete chimerism and GvHD development after allogeneic haematopoietic stem cell transplantation.

IF 2.7 3区 医学 Q3 ONCOLOGY
Marta Dratwa-Kuzmin, Piotr Lacina, Barbara Wysoczanska, Dorota Kilinska, Jagoda Siemaszko, Malgorzata Sobczyk-Kruszelnicka, Wojciech Fidyk, Iwona Solarska, Barbara Nasiłowska-Adamska, Patrycja Skowronska, Maria Bieniaszewska, Agnieszka Tomaszewska, Grzegorz Basak, Sebastian Giebel, Katarzyna Bogunia-Kubik
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Abstract

Introduction: Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase that maintains genome stability by maintaining telomere length (TL). The massive proliferation of donor cells in the recipient's body for engraftment results in accelerated telomere shortening. Genetic variability within the TERT gene affects telomerase activity, and was shown to influence of haematopoietic stem cell transplantation (HSCT) outcome. In the present study, we aimed to analyse the effect of recipient and donor TL and TERT single nucleotide polymorphism (SNP) on the occurrence of post-HSCT complications.

Methods: Our study included 120 recipient-donor pairs. TERT promoter (TERTp) SNP (rs2853669) SNP variant was detected with the use of the LightSNiP typing assay employing real-time polymerase chain reaction (PCR) amplifications. Telomere length measurements were performed using qPCR test kits (ScienCell's Absolute Human Telomere Length Quantification qPCR Assay Kit [AHTLQ], Carlsbad, CA, USA).

Results: The presence of TERTp rs2853669 T allele in the recipient was associated with a higher risk for acute graft-versus-host-disease (aGvHD) manifestation (p = 0.046) and a significantly shorter aGvHD-free survival (p = 0.041). The latter association was further confirmed in a Cox proportional hazards model (p = 0.043). However, no statistically significant association between telomere length and post-transplant complications was observed. Furthermore, we found that shorter TL characterized donors of patients with late complete chimerism at 180 day after HSCT (p = 0.011).

Conclusion: Our results suggest that recipient allele TERTp rs2853669 T is a marker of unfavourable outcome in the context of aGvHD. Shorter TL in donors could be associated with later achievement of complete chimerism.

端粒长度和端粒酶逆转录酶基因多态性是同种异体造血干细胞移植后完全嵌合和GvHD发生的潜在标志。
端粒酶逆转录酶(TERT)是端粒酶的催化亚基,通过维持端粒长度(TL)来维持基因组的稳定性。供体细胞在受体体内大量增殖用于移植,导致端粒加速缩短。TERT基因内的遗传变异影响端粒酶活性,并被证明影响造血干细胞移植(HSCT)的结果。在本研究中,我们旨在分析受体和供体TL和TERT单核苷酸多态性(SNP)对hsct后并发症发生的影响。方法:本研究纳入120对受者-供者配对。TERT启动子(TERTp) SNP (rs2853669) SNP变异采用实时聚合酶链反应(PCR)扩增的LightSNiP分型法检测。端粒长度测量使用qPCR检测试剂盒(ScienCell的绝对人类端粒长度定量qPCR检测试剂盒[AHTLQ],卡尔斯巴德,加利福尼亚州,美国)。结果:受体中TERTp rs2853669t等位基因的存在与急性移植物抗宿主病(aGvHD)表现的高风险(p = 0.046)和显著缩短无aGvHD生存期(p = 0.041)相关。后一种关联在Cox比例风险模型中得到进一步证实(p = 0.043)。然而,端粒长度与移植后并发症之间没有统计学意义的关联。此外,我们发现移植后180天晚期完全嵌合患者的供体TL较短(p = 0.011)。结论:我们的研究结果表明,受体等位基因TERTp rs2853669t是aGvHD背景下不利结果的标志。供体较短的TL可能与较晚实现完全嵌合有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.00
自引率
2.80%
发文量
577
审稿时长
2 months
期刊介绍: The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.
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