{Reference Type}: Journal Article
{Title}: ActivinA modulates B-acute lymphoblastic leukaemia cell communication and survival by inducing extracellular vesicles production.
{Author}: Licari E;Cricrì G;Mauri M;Raimondo F;Dioni L;Favero C;Giussani A;Starace R;Nucera S;Biondi A;Piazza R;Bollati V;Dander E;D'Amico G;
{Journal}: Sci Rep
{Volume}: 14
{Issue}: 1
{Year}: 2024 07 12
{Factor}: 4.996
{DOI}: 10.1038/s41598-024-66779-3
{Abstract}: 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.