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慢性移植物抗宿主病中可靶向药物的诊断、预后和预测生物标志物的寻找。

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease.

机构信息

a Department of Pediatrics , Indiana University , Indianapolis , IN , USA.

b Department of Microbiology Immunology , Indiana University , Indianapolis , IN , USA.

出版信息

Expert Rev Clin Immunol. 2018 May;14(5):389-404. doi: 10.1080/1744666X.2018.1463159. Epub 2018 Apr 19.

DOI:10.1080/1744666X.2018.1463159
PMID:29629613
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6017989/
Abstract

Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers. Areas covered: This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed. Expert commentary: We focus on biomarkers that play an essential role in target identification.

摘要

慢性移植物抗宿主病(cGVHD)仍是异基因造血干细胞移植(allo-HSCT)后晚期发病和死亡的主要原因,allo-HSCT 是治疗良性和恶性血液系统疾病的一种越来越常用的治愈方法。生物标志物的鉴定对于开发非侵入性、具有成本效益的 cGVHD 诊断、预后和预测性检测方法至关重要,这些方法可用于临床。此外,生物标志物可能有助于深入了解正在进行的病理生理过程。最近,包括基因组学、转录组学、蛋白质组学和细胞组学在内的组学技术的广泛应用为发现新的生物标志物提供了机会。

涵盖领域

本综述重点介绍了通过组学技术鉴定的生物标志物,这些标志物在药物开发的靶点识别中起着关键作用,并且在至少两个独立队列中得到了验证。它还总结了目前用于识别这些有用的 cGVHD 靶点的组学工具的现状。我们简要列出了迄今为止已鉴定和验证的生物标志物。我们进一步讨论了与这些生物标志物的开发和应用相关的挑战,这些生物标志物可用于 cGVHD 患者的管理。最后,讨论了可作为药物靶点的生物标志物,这些标志物代表了潜在的治疗靶点。

专家评论

我们专注于在靶点识别中发挥重要作用的生物标志物。

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Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a novel biomarker in patients.鼠慢性移植物抗宿主病蛋白质组谱分析发现 CCL15 是患者的一种新型生物标志物。
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Phase 1 study of the Hedgehog pathway inhibitor sonidegib for steroid-refractory chronic graft-versus-host disease.
血管性血友病因子、因子 VIII 和其他急性期反应物作为慢性移植物抗宿主病中炎症和内皮功能障碍的生物标志物。
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Pathophysiology of Chronic Graft-versus-Host Disease and Therapeutic Targets.慢性移植物抗宿主病的病理生理学及治疗靶点
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CD56 natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft--host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results.粒细胞集落刺激因子预处理的供者血液或骨髓制品中的 CD56 自然杀伤细胞调节细胞可调节慢性移植物抗宿主病:加拿大血液和骨髓移植组 0601 随机研究结果。
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