Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
Semin Thromb Hemost. 2019 Oct;45(7):751-756. doi: 10.1055/s-0039-1692977. Epub 2019 Aug 12.
Clinicians and scientists in the fields of hemostasis and thrombosis have been among those first to integrate new molecular strategies for the purpose of enhancing disease diagnosis and treatment. The molecular diagnosis and introduction of gene therapy approaches for hemophilia are obvious examples of this tendency. In this review, the authors summarize information concerning three molecular technologies that have reached various stages of translational potential for their incorporation into the clinical management of disorders of hemostasis. Chromatin conformation assays are now being used to capture structural knowledge of long-range genomic interactions that can alter patterns of gene expression and contribute to quantitative trait pathogenesis. Liquid biopsies in various forms are providing opportunities for early cancer detection, and in the context of tumor-educated platelets, as described here, can also characterize tumor type and the extent of tumor progression. This technology is already being trialed in patients with unprovoked venous thrombosis to assess the potential for occult malignancies. Lastly, advances in single cell transcriptome analysis, provide opportunities to definitively determine molecular events in rare cells, such as antigen-specific regulatory T cells, within the context of heterogeneous cell populations.
止血和血栓形成领域的临床医生和科学家是最早将新的分子策略整合用于增强疾病诊断和治疗的人之一。血友病的分子诊断和基因治疗方法的引入就是这种趋势的明显例子。在这篇综述中,作者总结了三种分子技术的信息,这些技术已经达到了转化为止血障碍临床管理的不同阶段。染色质构象分析现在用于捕获可以改变基因表达模式并导致数量性状发病机制的长程基因组相互作用的结构知识。各种形式的液体活检为早期癌症检测提供了机会,并且如这里所述,在肿瘤教育血小板的背景下,也可以表征肿瘤类型和肿瘤进展程度。这项技术已经在不明原因的静脉血栓形成患者中进行了试验,以评估隐匿性恶性肿瘤的可能性。最后,单细胞转录组分析的进展为在异质细胞群体中确定罕见细胞(如抗原特异性调节 T 细胞)中的分子事件提供了机会。