血清细胞外囊泡衍生的小RNA作为非侵入性生物标志物在急性髓系白血病研究中的潜在作用。
The potential role of serum extracellular vesicle derived small RNAs in AML research as non-invasive biomarker.
作者信息
Li Lin, Mussack Veronika, Görgens André, Pepeldjiyska Elena, Hartz Anne Sophie, Aslan Hazal, Rackl Elias, Rank Andreas, Schmohl Jörg, El Andaloussi Samir, Pfaffl Michael W, Schmetzer Helga
机构信息
Immune-Modulation, Medical Department III, University Hospital of Munich Marchioninistraße 15 81377 Munich Germany
Department of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich Freising Germany
出版信息
Nanoscale Adv. 2023 Feb 20;5(6):1691-1705. doi: 10.1039/d2na00959e. eCollection 2023 Mar 14.
BACKGROUND
Extracellular vesicles (EV) are cell-derived vesicles released by all cells in health and disease. Accordingly, EVs are also released by cells in acute myeloid leukemia (AML), a hematologic malignancy characterized by uncontrolled growth of immature myeloid cells, and these EVs likely carry markers and molecular cargo reflecting the malignant transformation occurring in diseased cells. Monitoring antileukemic or proleukemic processes during disease development and treatment is essential. Therefore, EVs and EV-derived microRNA (miRNA) from AML samples were explored as biomarkers to distinguish disease-related patterns or .
METHODOLOGY
EVs were purified from serum of healthy (H) volunteers and AML patients by immunoaffinity. EV surface protein profiles were analyzed by multiplex bead-based flow cytometry (MBFCM) and total RNA was isolated from EVs prior to miRNA profiling small RNA sequencing.
RESULTS
MBFCM revealed different surface protein patterns in H AML EVs. miRNA analysis showed individual as well as highly dysregulated patterns in H and AML samples.
CONCLUSIONS
In this study, we provide a proof-of-concept for the discriminative potential of EV derived miRNA profiles as biomarkers in H AML samples.
背景
细胞外囊泡（EV）是健康和疾病状态下所有细胞释放的细胞衍生囊泡。因此，急性髓系白血病（AML）细胞也会释放EV，AML是一种以未成熟髓系细胞不受控制生长为特征的血液系统恶性肿瘤，这些EV可能携带反映病变细胞中发生的恶性转化的标志物和分子载荷。在疾病发展和治疗过程中监测抗白血病或促白血病过程至关重要。因此，对AML样本中的EV和EV衍生的微小RNA（miRNA）进行了探索，以作为区分疾病相关模式的生物标志物。
方法
通过免疫亲和从健康（H）志愿者和AML患者的血清中纯化EV。通过基于多重微珠的流式细胞术（MBFCM）分析EV表面蛋白谱，并在进行miRNA谱分析（小RNA测序）之前从EV中分离总RNA。
结果
MBFCM显示H和AML EV中存在不同的表面蛋白模式。miRNA分析显示H和AML样本中存在个体以及高度失调的模式。
结论
在本研究中，我们为EV衍生的miRNA谱作为H和AML样本中生物标志物的鉴别潜力提供了概念验证。
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