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成人双份脐血移植受者初始端粒长度及移植后变化的评估。

Evaluation of Initial Telomere Length and Changes after Transplantation in Adult Double-Unit Cord Blood Transplant Recipients.

作者信息

Ashbridge Beth, Zehir Ahmet, Lubin Marissa, Barker Juliet N, Moore Malcolm A S

机构信息

Cell Biology Program, Sloan-Kettering Institute, New York, New York.

Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, New York.

出版信息

Biol Blood Marrow Transplant. 2015 Jul;21(7):1334-6. doi: 10.1016/j.bbmt.2015.04.006. Epub 2015 Apr 10.

DOI:10.1016/j.bbmt.2015.04.006
PMID:25865647
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4466009/
Abstract

Cord blood (CB) leukocytes have inherent telomere length (TL) variation, and CB hematopoietic stem cells (HSC) can maintain high telomerase levels preventing telomere attrition in vitro. We evaluated TL changes in 13 adult double-unit CB transplant (CBT) recipients. In the 26 units, we observed a marked variation in CB TL at thaw (median, 9.99 kilobases [kb]; range, 6.85 to 13.5). All 13 patients engrafted. Of 11 engrafting with 1 unit, there was no correlation between unit dominance and TL (mean dominant unit TL, 8.84 kb ± 1.76; mean nonengrafting unit TL, 10.3 kb ± 1.81; P = .77). Serial measurements of TL up to 1 year after CBT demonstrated an overall mean 3.04 kb ± .16 TL decrease with only 1 patient exhibiting telomere maintenance. In summary, initial TL does not predict CB unit dominance. Moreover, our analysis suggests neonatal hematopoiesis makes a transition to an HSC characterized by changes in average TL and potentially low telomerase asymmetric cell division in adult CBT recipients. Further investigation of alterations in telomere length and its clinical implications after transplantation of this observation are indicated.

摘要

脐血(CB)白细胞具有固有的端粒长度(TL)变异,并且CB造血干细胞(HSC)能够维持较高的端粒酶水平,从而在体外防止端粒磨损。我们评估了13例成人双单位脐血移植(CBT)受者的TL变化。在这26个单位中,我们观察到解冻时CB TL存在显著差异(中位数为9.99千碱基[kb];范围为6.85至13.5)。所有13例患者均实现植入。在11例接受1个单位植入的患者中,单位优势与TL之间无相关性(优势单位平均TL为8.84 kb±1.76;非植入单位平均TL为10.3 kb±1.81;P = 0.77)。CBT后长达1年的TL连续测量显示,总体平均TL下降3.04 kb±0.16,只有1例患者表现出端粒维持。总之,初始TL不能预测CB单位优势。此外,我们的分析表明,新生儿造血向一种HSC转变,其特征是成年CBT受者的平均TL发生变化,并且可能存在端粒酶不对称细胞分裂较低的情况。需要对这一观察结果在移植后端粒长度的改变及其临床意义进行进一步研究。

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本文引用的文献

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Biol Blood Marrow Transplant. 2013 Jun;19(6):904-11. doi: 10.1016/j.bbmt.2013.02.008. Epub 2013 Feb 14.
2
A novel reduced-intensity conditioning regimen induces a high incidence of sustained donor-derived neutrophil and platelet engraftment after double-unit cord blood transplantation.一种新型的低强度预处理方案可在双份脐血移植后诱导供者来源的中性粒细胞和血小板持续植入。
Biol Blood Marrow Transplant. 2013 May;19(5):799-803. doi: 10.1016/j.bbmt.2013.02.007. Epub 2013 Feb 14.
3
Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts.输注细胞剂量和 HLA 配型对双份脐血移植后植入的影响。
Blood. 2011 Mar 24;117(12):3277-85; quiz 3478. doi: 10.1182/blood-2010-08-300491. Epub 2010 Dec 13.
4
A "no-wash" albumin-dextran dilution strategy for cord blood unit thaw: high rate of engraftment and a low incidence of serious infusion reactions.一种无需洗涤的白蛋白-葡聚糖稀释策略用于脐血单位解冻:高植入率和低严重输注反应发生率。
Biol Blood Marrow Transplant. 2009 Dec;15(12):1596-602. doi: 10.1016/j.bbmt.2009.08.009. Epub 2009 Sep 25.
5
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Blood. 2005 Feb 1;105(3):1343-7. doi: 10.1182/blood-2004-07-2717. Epub 2004 Oct 5.
6
Elevated telomerase activity and minimal telomere loss in cord blood long-term cultures with extensive stem cell replication.在具有广泛干细胞复制的脐血长期培养物中,端粒酶活性升高且端粒损失最小。
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