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

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.