High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders
High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders
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DOI：
10.1007/s13277-015-3741-3
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发表时间：
2015-12-01
期刊：
影响因子：
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通讯作者：
Del Vecchio, Luigi
中科院分区：
文献类型：
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作者：
Caivano, Antonella;Laurenzana, Ilaria;Del Vecchio, Luigi
许多细胞类型释放细胞外囊泡（EVs），包括外泌体、微囊泡（MVs）和凋亡小体，它们在生理和疾病中发挥作用。血液恶性肿瘤（HMs）中循环ev的存在和表型在很大程度上仍未被研究。本研究的目的是将HM患者的外周血EVs与健康受试者（对照组）进行比较。我们从慢性淋巴细胞白血病（CLL）、非霍奇金淋巴瘤（NHL）、Waldenstrom巨球蛋白血症（WM）、霍奇金淋巴瘤（HL）、多发性骨髓瘤（MM）、急性髓性白血病（AML）、骨髓增生性肿瘤（mpn）、骨髓增生异常综合征（MDS）和对照组患者中分离血清ev。采用超离心步骤从外周血血清中分离EVs，流式细胞术分析EVs的计数、大小和免疫表型。与健康对照相比，在WM、HL、MM、AML和一些mpn中，MV水平显著升高，而在CLL和NHL中，MV水平的升高程度较低。与对照相比，HL、MM和mpn产生的mv群体的特征是体积较小（小于0.3 μ m）。来自患者的mv特异性表达肿瘤相关抗原，如B细胞肿瘤中的CD19、MM中的CD38、髓系肿瘤中的CD13和HL中的CD30。MVs的总数和抗原特异性计数与不同临床特征（如CLL的Rai分期、WM的国际预后评分系统、MM的国际分期系统、HL的临床分期）均显著相关。mv可能是HMs中一种新的生物标志物。
Many cell types release extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, which play a role in physiology and diseases. Presence and phenotype of circulating EVs in hematological malignancies (HMs) remain largely unexplored.The aim of this study was to characterize EVs in peripheral blood of HM patients compared to healthy subjects (controls). We isolated serum EVs from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Waldenstrom's macroglobulinemia (WM), Hodgkin's lymphoma (HL), multiple myeloma (MM), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and controls. EVs were isolated from serum of peripheral blood by ultracentrifuge steps and analyzed by flow cytometry to define count, size, and immunophenotype. MV levels were significantly elevated in WM, HL, MM, AML, and some MPNs and, though at a lesser degree, in CLL and NHL as compared to healthy controls. HL, MM, and MPNs generated a population of MVs characterized by lower size (below 0.3 mu m) when compared to controls. MVs from patients specifically expressed tumor-related antigens, such as CD19 in B cell neoplasms, CD38 in MM, CD13 in myeloid tumors, and CD30 in HL. Both total and antigen-specific count of MVs significantly correlated with different HM clinical features such as Rai stage in CLL, International Prognostic Scoring System in WM, International Staging System in MM, and clinical stage in HL. MVs may represent a novel biomarker in HMs.