急性髓性白血病是一组恶性血液疾病，其起源于造血前体细胞的克隆过度增殖和分化失败，导致原始细胞在骨髓中积聚。间充质基质细胞（MSC）已被证明通过直接和间接相互作用对肿瘤细胞发挥多种作用。外泌体作为间接细胞间通讯的手段之一，由包括间充质干细胞在内的不同类型的细胞释放，其不同的内容物，如lncRNA，使其能够对靶细胞产生显着的影响。我们的研究旨在研究 BM-MSC 外泌体对 HL-60 AML 细胞的细胞和分子特征的影响，特别是检测与 AML 白血病发生、细胞生长、耐药性和不良预后相关的 lncRNA 表达的变化。用无血清培养基培养 BM-MSC，从其上清液中分离出外泌体。外泌体的验证分三个阶段进行：使用 TEM 进行形态分析、使用 DLS 进行大小评估以及使用流式细胞术进行 CD 标记鉴定。随后，用分离的 BM-MSC 外泌体处理 HL-60 AML 细胞，以确定其内容物对白血病细胞的影响。通过MTT测定评估细胞代谢活性，通过流式细胞术评估细胞周期进展、凋亡、ROS水平和增殖。此外，还进行了 RT-qPCR 来测定 lncRNA 以及凋亡、ROS 和细胞周期相关基因的表达水平。 MTT 测定和流式细胞术分析表明 BM-MSC 外泌体显着抑制细胞代谢活性、增殖和细胞周期进程。此外，这些外泌体可以有效增加 HL-60 细胞的凋亡和 ROS 水平。 p53、p21、BAX 和 FOXO4 的表达水平升高，而 BCL2 和 c-Myc 水平降低。与未处理的细胞相比，经处理的 HL-60 细胞中的 MALAT1、HOTAIR 和 H19 表达水平也显着降低。 BM-MSC 外泌体可能通过降低 MALAT1、HOTAIR 和 H19 的表达水平来抑制细胞周期进程、增殖和代谢活动，同时提高 HL-60 细胞中的 ROS 指数和凋亡率。这些发现表明 BM-MSC 外泌体可能作为白血病的潜在支持疗法。© 2024。作者。

Acute myeloid leukemia represents a group of malignant blood disorders that originate from clonal over-proliferation and the differentiation failure of hematopoietic precursors, resulting in the accumulation of blasts in the bone marrow. Mesenchymal stromal cells (MSCs) have been shown to exert diverse effects on tumor cells through direct and indirect interaction. Exosomes, as one of the means of indirect intercellular communication, are released from different types of cells, including MSCs, and their various contents, such as lncRNAs, enable them to exert significant impacts on target cells. Our study aims to investigate the effects of BM-MSC exosomes on the cellular and molecular characterization of HL-60 AML cells, particularly detecting the alterations in the expression of lncRNAs involved in AML leukemogenesis, cell growth, drug resistance, and poor prognosis. BM-MSCs were cultured with serum-free culture media to isolate exosomes from their supernatants. The validation of exosomes was performed in three stages: morphological analysis using TEM, size evaluation using DLS, and CD marker identification using flow cytometry. Subsequently, the HL-60 AML cells were treated with isolated BM-MSC exosomes to determine the impact of their contents on leukemic cells. Cell metabolic activity was evaluated by the MTT assay, while cell cycle progression, apoptosis, ROS levels, and proliferation were assessed by flow cytometry. Furthermore, RT-qPCR was conducted to determine the expression levels of lncRNAs and apoptosis-, ROS-, and cell cycle-related genes. MTT assay and flow cytometry analysis revealed that BM-MSC exosomes considerably suppressed cell metabolic activity, proliferation, and cell cycle progression. Also, these exosomes could effectively increase apoptosis and ROS levels in HL-60 cells. The expression levels of p53, p21, BAX, and FOXO4 were increased, while the BCL2 and c-Myc levels decreased. MALAT1, HOTAIR, and H19 expression levels were also significantly decreased in treated HL-60 cells compared to their untreated counterparts. BM-MSC exosomes suppress cell cycle progression, proliferation, and metabolic activity while simultaneously elevating the ROS index and apoptosis ratio in HL-60 cells, likely by reducing the expression levels of MALAT1, HOTAIR, and H19. These findings suggest that BM-MSC exosomes might serve as potential supportive therapies for leukemia.© 2024. The Author(s).