Kinetics of DNases after hematopoietic stem cell transplant

Blood Vessels, Thrombosis & Hemostasis Pub Date : 2025-01-20 DOI:10.1016/j.bvth.2025.100055

Azada Ibrahimova , Nathan Luebbering , Lucille Langenberg , Sheyar Abdullah , Lauren Strecker , Kelly E. Lake , Adam Lane , Aaron Webster , Kasiani C. Myers , Sonata Jodele , Stella M. Davies

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Abstract

The entire hematopoietic system is rapidly lysed over 8 to 10 days during hematopoietic stem cell transplant (HSCT), releasing toxic intracellular molecules such as cell-free DNA (cfDNA) and proteins such as actin into the circulation. Neutrophil extracellular traps released at the time of engraftment also contribute to the cfDNA burden. Clearance of cfDNA is essential for limiting tissue toxicity. We measured levels of cfDNA, DNase I and DNase1L3 in 108 consecutive patients receiving allogeneic HSCT at baseline and on days 0, 7, 14, 30, and 100. cfDNA levels peak at day 14 and are higher in patients with endothelial injury. DNase I levels are depleted on day 7, recovering quickly by day 14, and remain above baseline at day 100. DNase1L3 levels decreased below baseline at day 0, reached a nadir by day 7, but recovered by day 30 remaining above baseline at day 100. Patients with a periengraftment oxygen requirement and those with transplant-associated thrombotic microangiopathy had higher DNase I levels than those without. DNase1L3 levels did not influence any HSCT outcomes. We analyzed DNase I activity using plasmid DNA degradation and showed decreased activity on days 0 and 7, in agreement with reduced protein levels. Further studies are needed to understand the dynamics of DNases in patients undergoing HSCT, to assess their potential role in HSCT toxicities.

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造血干细胞移植后的 DN 酶动力学

在造血干细胞移植（HSCT）过程中，整个造血系统在8 ~ 10天内被快速分解，释放出细胞内有毒分子，如游离DNA （cfDNA）和蛋白质，如肌动蛋白进入循环。植入时释放的中性粒细胞胞外陷阱也有助于cfDNA负担。清除cfDNA对限制组织毒性至关重要。我们测量了108例连续接受同种异体造血干细胞移植的患者在基线和第0、7、14、30和100天的cfDNA、DNase I和DNase1L3水平。cfDNA水平在第14天达到峰值，内皮损伤患者的cfDNA水平更高。DNase I水平在第7天耗尽，在第14天迅速恢复，并在第100天保持高于基线。DNase1L3水平在第0天低于基线，在第7天达到最低点，但在第30天恢复，并在第100天高于基线。移植前后需要氧气的患者和移植相关血栓性微血管病患者的DNase I水平高于没有需要氧气的患者。DNase1L3水平不影响任何HSCT结果。我们用质粒DNA降解法分析了DNA酶I的活性，结果显示，在第0天和第7天，DNA酶I的活性下降，与蛋白质水平下降一致。需要进一步的研究来了解接受HSCT患者的dna酶的动态，以评估它们在HSCT毒性中的潜在作用。

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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Blood Vessels, Thrombosis & Hemostasis

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