Application of platelet transcriptomics for assessing treatment effectiveness and predicting long-term platelet counts recovery in aplastic anemia.

IF 5.5 2区 医学 Q1 HEMATOLOGY
Jin Mao, Jingyu Zhao, Hong Pan, Zhen Gao, Lele Zhang, Weiwang Li, Liwei Fang, Cuicui Liu, Pei Su, Hongtao Wang, Jiaxi Zhou, Jun Shi
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Abstract

Background: Aplastic anemia (AA) is a bone marrow failure disease for which the means of assessing and predicting the therapeutic effectiveness are still relatively limited. Thrombocytopenia is often the earliest and most severe symptom in patients newly diagnosed with AA. While clinical consideration is usually given to the quantitative changes in platelets during treatment, there is little focus on the resolution of the molecular characteristics of platelets in AA.

Objectives: To investigate the changes in platelet molecular characteristics throughout the treatment process of AA, and to explore the use of transcriptomics for monitoring and predicting treatment outcomes.

Methods: We comprehensively analyzed platelet transcriptomic changes in patients with AA at initial diagnosis and different stages of treatment effectiveness using bulk transcriptome sequencing.

Results: Genes associated with cell proliferation, erythroid function, and amino acid transport were elevated in newly diagnosed AA. Conversely, genes linked to histones, thrombopoiesis, mitochondrial energy metabolism, and signaling pathways were significantly downregulated. Additionally, 60.6% of the differentially expressed genes were substantially restored following complete remission. Furthermore, through the examination of longitudinal samples, we identified recovery ascending genes that could serve as viable biomarkers for assessing treatment effectiveness in AA. Besides, we observed that higher expression levels of recovery ascending genes may predict superior long-term platelet counts recovery 6 months in advance in patients with partial response.

Conclusion: The platelet transcriptome undergoes profound changes and can serve as a potential indicator for assessing treatment effectiveness and predicting long-term platelet counts recovery in AA.

应用血小板转录组学评估再生障碍性贫血的治疗效果并预测血小板计数的长期恢复情况。
背景:再生障碍性贫血(AA)是一种骨髓衰竭疾病:再生障碍性贫血(AA)是一种骨髓衰竭疾病,其治疗效果的评估和预测手段仍然相对有限。血小板减少通常是新诊断为再生障碍性贫血(Dx-AA)的患者最早出现且最严重的症状。临床上通常考虑治疗过程中血小板的数量变化,但很少关注 AA 患者血小板分子特征的变化:研究AA治疗过程中血小板分子特征的变化,并探索利用转录组学监测和预测治疗结果:方法:我们利用批量转录组测序技术全面分析了AA患者在最初诊断和不同治疗效果阶段的血小板转录组变化:结果:与细胞增殖、红细胞功能和氨基酸转运相关的基因在Dx-AA中升高。相反,与组蛋白、血栓形成、线粒体能量代谢和信号通路相关的基因则明显下调。完全缓解后,60.6%的差异表达基因得到了大幅恢复。此外,通过对纵向样本的研究,我们发现了可作为评估 AA 治疗效果的生物标志物的恢复上升基因(RAG)。此外,我们还观察到,较高的 RAG 表达水平可提前 6 个月预示部分反应患者的血小板计数会有较好的长期恢复:血小板转录组发生了深刻变化,可作为评估治疗效果和预测 AA 患者血小板计数长期恢复的潜在指标。
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来源期刊
Journal of Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis 医学-外周血管病
CiteScore
24.30
自引率
3.80%
发文量
321
审稿时长
1 months
期刊介绍: The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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