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Isolation of Human CD138+ Microparticles from the Plasma of Patients with Multiple Myeloma

机译:从多发性骨髓瘤患者血浆中分离人CD138 +微粒

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摘要

The confinement of multiple myeloma (MM) to the bone marrow microenvironment requires an invasive bone marrow biopsy to monitor the malignant compartment. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity mainly because they indirectly measure tumor burden inside the bone marrow and fail to capture the patchy, multisite tumor infiltrates associated with MM. Microparticles (MPs) are 0.1- to 1.0-μm membrane vesicles, which contain the cellular content of their originating cell. MPs are functional mediators and convey prothrombotic, promalignant, proresistance, and proinflammatory messages, establishing intercellular cross talk and bypassing the need for direct cell-cell contact in many pathologies. In this study, we analyzed plasma cell–derived MPs (CD138+) from deidentified MM patients (n = 64) and normal subjects (n = 18) using flow cytometry. The morphology and size of the MPs were further analyzed using scanning electron microscopy. Our study shows the proof of a systemic signature of MPs in MM patients. We observed that the levels of MPs were significantly elevated in MM corresponding to the tumor burden. We provide the first evidence for the presence of MPs in the peripheral blood of MM patients with potential applications in personalized MM clinical monitoring.
机译:多发性骨髓瘤(MM)仅限于骨髓微环境,需要进行侵入性骨髓活检以监测恶性区室。用于确定治疗反应和肿瘤复发的现有临床工具的敏感性受到限制,主要是因为它们间接测量骨髓内的肿瘤负荷并且无法捕获与MM相关的斑片状,多部位肿瘤浸润。微粒(MPs)是0.1-1.0μm的膜囊泡,包含其原始细胞的细胞含量。 MP是功能性介质,可传递血栓形成,恶变,抵抗和促炎信息,建立细胞间串扰并绕开许多病理学中直接细胞接触的需要。在这项研究中,我们使用流式细胞仪分析了身份不明的MM患者(n = 64)和正常受试者(n = 18)的浆细胞来源MP(CD138 + )。使用扫描电子显微镜进一步分析MP的形态和大小。我们的研究显示了MM患者中MP的系统性签名的证据。我们观察到,与肿瘤负荷相对应,MM中MPs水平显着升高。我们为MM患者外周血中MP的存在提供了第一个证据,并可能在个性化MM临床监测中应用。

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