细胞外囊泡（EV）是一种新的细胞通讯机制，通过将其货物递送到靶细胞中来调节分子途径。 EV 介导的串扰有助于肿瘤存活和抵抗细胞应激。然而，EV 在 B 细胞急性淋巴细胞白血病 (B-ALL) 中的作用仍有待彻底研究。我们最近发表了 ActivinA 可以增加 B-ALL 细胞中细胞内钙水平并促进肌动蛋白聚合。这些生物过程指导细胞骨架重组，这是 EV 分泌和内化的关键事件。因此，我们研究了 EV 在 B-ALL 中的作用以及 ActivinA 对这种现象的影响。我们证明白血病细胞响应 ActivinA 治疗释放更多数量的 EV，并且它们可以主动摄取其他 B-ALL 细胞释放的 EV。在培养诱导的应激条件下，EV共培养以剂量依赖性方式促进B-ALL细胞的细胞存活。用 ActivinA 或从 ActivinA 刺激的细胞中分离出的 EV 直接刺激 B-ALL 细胞在预防细胞死亡方面甚至更有效。这种效应可能归因于 ActivinA 诱导的囊泡形成和 EV 相关 microRNA 修饰的增加。这些数据表明，ActivinA 可以增强 EV 介导的 B-ALL 串扰，从而提高应激条件下白血病的生存率。© 2024。作者。

Extracellular vesicles (EVs) are a new mechanism of cellular communication, by delivering their cargo into target cells to modulate molecular pathways. EV-mediated crosstalk contributes to tumor survival and resistance to cellular stress. However, the role of EVs in B-cell Acute Lymphoblastic Leukaemia (B-ALL) awaits to be thoroughly investigated. We recently published that ActivinA increases intracellular calcium levels and promotes actin polymerization in B-ALL cells. These biological processes guide cytoskeleton reorganization, which is a crucial event for EV secretion and internalization. Hence, we investigated the role of EVs in the context of B-ALL and the impact of ActivinA on this phenomenon. We demonstrated that leukemic cells release a higher number of EVs in response to ActivinA treatment, and they can actively uptake EVs released by other B-ALL cells. Under culture-induced stress conditions, EVs coculture promoted cell survival in B-ALL cells in a dose-dependent manner. Direct stimulation of B-ALL cells with ActivinA or with EVs isolated from ActivinA-stimulated cells was even more effective in preventing cell death. This effect can be possibly ascribed to the increase of vesiculation and modifications of EV-associated microRNAs induced by ActivinA. These data demonstrate that ActivinA boosts EV-mediated B-ALL crosstalk, improving leukemia survival in stress conditions.© 2024. The Author(s).