Journal Article

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

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

2025

Overview

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 ( TERT p) 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 TERT p 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 TERT p 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.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V,Springer
• Subject: Acute graft-versus-host-disease / Adolescent / Adult / Alleles / Allogeneic haematopoietic stem cell transplantation / Cancer Research / Cell proliferation / cell transplantation / Chimerism / Complete chimerism / Donors / Female / Gene polymorphism / Genetic variability / genetic variation / Graft vs Host Disease - etiology / Graft vs Host Disease - genetics / Graft-versus-host reaction / Hematology / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic stem cells / Humans / Internal Medicine / Male / Medicine / Medicine & Public Health / Middle Aged / Oncology / Polymerase chain reaction / Polymorphism / Polymorphism, Single Nucleotide / protein subunits / quantitative polymerase chain reaction / risk / RNA-directed DNA polymerase / Single-nucleotide polymorphism / Statistical analysis / Stem cell transplantation / Telomerase / Telomerase - genetics / Telomerase reverse transcriptase / Telomere - genetics / Telomere length / Telomeres / TERT gene / Transplantation Chimera - genetics / Transplantation, Homologous / Young Adult