Center of Human Development and Aging, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, United States.
Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands.
Front Immunol. 2022 Oct 3;13:966301. doi: 10.3389/fimmu.2022.966301. eCollection 2022.
The age of allogeneic hematopoietic cell transplant (HCT) donors and their hematopoietic cell telomere length (TL) might affect recipients' outcomes. Our goals were to examine the possible effect of these donors' factors on the recipients' hematopoietic cell TL and quantify hematopoietic cell TL shortening in the critical first three-month post-HCT. We measured hematopoietic cell TL parameters in 75 recipient-donor pairs, from the Blood and Marrow Transplant Clinical Trials Network (protocol#1202), by Southern blotting (SB), the Telomeres Shortest Length Assay (TeSLA), and quantitative PCR (qPCR). Recipients' hematopoietic cell TL parameters post-HCT correlated with donors' age (p<0.001 for all methods), but not recipients' own age, and with donors' pre-HCT hematopoietic cell TL (p<0.0001 for all). Multivariate analyses showed that donors' hematopoietic cell TL pre-HCT, independent of donors' age, explained most of the variability in recipients' hematopoietic cell TL post-HCT (81% for SB, 56% for TeSLA, and 65% for qPCR; p>0.0001 for all). SB and TeSLA detected hematopoietic cell TL shortening in all recipients post-HCT (mean=0.52kb and 0.47kb, respectively; >15-fold the annual TL shortening in adults; p<0.00001 for both), but qPCR detected shortening only in 57.5% of recipients. TeSLA detected a buildup of post-HCT of telomeres <3 kb in 96% of recipients (p<0.0001). In conclusion, HCT decouples hematopoietic cell TL in the recipients from their own age to reflect the donors' age. The potential donors' age effect on outcomes of HCT might be partially mediated by short hematopoietic cell TL in older donors. qPCR-based TL measurement is suboptimal for detecting telomere shortening post-HCT.
异基因造血细胞移植（HCT）供者的年龄及其造血细胞端粒长度（TL）可能会影响受者的结果。我们的目标是研究这些供者因素对受者造血细胞 TL 的可能影响，并量化 HCT 后关键的前三个月内造血细胞 TL 的缩短情况。我们通过 Southern 印迹（SB）、端粒最短长度测定法（TeSLA）和定量 PCR（qPCR）测量了来自血液和骨髓移植临床研究网络（方案#1202）的 75 对受者-供者的造血细胞 TL 参数。HCT 后受者的造血细胞 TL 参数与供者的年龄相关（所有方法的 p<0.001），但与受者自身年龄无关，与供者 HCT 前的造血细胞 TL 相关（所有方法的 p<0.0001）。多变量分析显示，供者 HCT 前的造血细胞 TL，独立于供者年龄，解释了受者 HCT 后造血细胞 TL 的大部分变异性（SB 为 81%，TeSLA 为 56%，qPCR 为 65%；所有方法的 p>0.0001）。SB 和 TeSLA 在所有受者 HCT 后均检测到造血细胞 TL 缩短（平均分别为 0.52kb 和 0.47kb，超过成年人每年 TL 缩短的 15 倍；p<0.00001 均），但 qPCR 仅在 57.5%的受者中检测到缩短。TeSLA 在 96%的受者中检测到 HCT 后端粒<3kb 的堆积（p<0.0001）。总之，HCT 将受者的造血细胞 TL 与其自身年龄解耦，反映供者的年龄。潜在供者年龄对 HCT 结果的影响可能部分是由年龄较大的供者中造血细胞 TL 较短介导的。基于 qPCR 的 TL 测量对于检测 HCT 后端粒缩短并不理想。
