Abstract：
Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP-ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV-marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP-ALL patients. The EV proteome of primary BCP-ALL cell-derived EVs were compared against EVs from healthy donor B cells and the BCP-ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP-ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP-ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers.
摘要：
急性小儿白血病是通过对母细胞的骨髓穿刺物评估来诊断和监测的，以衡量微小残留疾病。血液样本形式的液体活检可以大大减少侵入性骨髓穿刺的需求，但是目前没有与骨髓诊断敏感性相匹配的血液标志物。循环细胞外囊泡（EV）代表候选生物标志物，可能反映骨髓中的爆炸负荷，一些研究报道了电动汽车作为成人血液恶性肿瘤生物标志物的实用性。据报道，几种血液恶性肿瘤的电动汽车水平升高，我们在此类似地报道了儿科BCP-ALL患者血浆中EV浓度升高。血浆EV在细胞来源方面非常异质，因此,鉴定癌症选择性EV标志物具有挑战性.这里,我们采用还原性方法来鉴定与源自BCP-ALL患者的血浆EV选择性相关的蛋白标志物.将原代BCP-ALL细胞衍生的EV蛋白质组与来自健康供体B细胞和BCP-ALL细胞系REH的EV进行比较，并进一步针对从健康儿科供体和儿科BCP-ALL患者血浆中分离出的EV。通过这种方法，我们鉴定了6种蛋白质(CD317，CD38，IGF2BP1，PCNA，CSDE1和GPR116)仅在BCP-ALL衍生的电动汽车中明确鉴定，而在健康对照电动汽车中不明确，可以用作诊断生物标志物。
