文章：

初诊急性髓系白血病患者骨髓穿刺样本中髓系细胞胚胎抗原及其信号通路的高维质谱流式分析

High-Dimensional Mass Cytometry Analysis of Embryonic Antigens and Their Signaling Pathways in Myeloid Cells from Bone Marrow Aspirates in AML Patients at Diagnosis

原文发布日期：25 September 2023

DOI: 10.3390/cancers15194707

类型: Article

开放获取: 是

英文摘要：

Background: Embryonic antigens (EA) regulate pluripotency, self-renewal, and differentiation in embryonic stem (ES) cells during their development. In adult somatic cells, EA expression is normally inhibited; however, EAs can be re-expressed by cancer cells and are involved in the deregulation of different signaling pathways (SPs). In the context of AML, data concerning the expression of EAs are scarce and contradictory. Methods: We used mass cytometry to explore the expression of EAs and three SPs in myeloid cells from AML patients and normal bone marrow (NBM). Imaging flow cytometry was used for morphological assessment of cells in association with their OCT3/4 expression status (positive vs. negative). Results: An overall reduction in or absence of EA expression was observed in immature myeloid cells from AML patients compared to their normal counterparts. Stage-specific embryonic antigen-3 (SSEA-3) was consistently expressed at low levels in immature myeloid cells, whereas SSEA-1 was overexpressed in hematopoietic stem cells (HSCs) and myeloblasts from AML with monocytic differentiation (AML M4/M5). Therefore, these markers are valuable for distinguishing between normal and abnormal myeloid cells. These preliminary results show that the exploration of myeloid cell intracellular SPs in the setting of AML is very informative. Deregulation of three important leukemogenic SPs was also observed in myeloid cells from AML. Conclusions: Exploring EAs and SPs in myeloid cells from AML patients by mass cytometry may help identify characteristic phenotypes and facilitate AML follow-up.

摘要翻译： 

背景：胚胎抗原（EA）在胚胎干细胞（ES）发育过程中调控其多能性、自我更新与分化。在成体体细胞中，胚胎抗原的表达通常受到抑制；然而，癌细胞可重新表达胚胎抗原，并参与多种信号通路（SPs）的失调。在急性髓系白血病（AML）中，关于胚胎抗原表达的数据既稀缺又存在矛盾。方法：我们采用质谱流式细胞术检测AML患者与正常骨髓（NBM）来源的髓系细胞中胚胎抗原及三种信号通路的表达情况。通过成像流式细胞术对细胞进行形态学评估，并结合其OCT3/4表达状态（阳性与阴性）进行分析。结果：与正常髓系细胞相比，AML患者的未成熟髓系细胞中胚胎抗原表达普遍降低或缺失。阶段特异性胚胎抗原-3（SSEA-3）在未成熟髓系细胞中持续低水平表达，而SSEA-1在伴有单核细胞分化的AML（AML M4/M5）的造血干细胞（HSCs）及原始粒细胞中过度表达。因此，这些标志物对区分正常与异常髓系细胞具有重要价值。初步结果表明，在AML背景下探索髓系细胞内信号通路具有重要信息价值。在AML髓系细胞中还观察到三种重要致白血病信号通路的失调。结论：通过质谱流式细胞术探索AML患者髓系细胞中的胚胎抗原与信号通路，有助于识别特征性表型，并为AML的随访监测提供便利。

原文链接：

High-Dimensional Mass Cytometry Analysis of Embryonic Antigens and Their Signaling Pathways in Myeloid Cells from Bone Marrow Aspirates in AML Patients at Diagnosis