ActivinA Modulates B-acute Lymphoblastic Leukaemia Cell Communication and Survival by Inducing Extracellular Vesicles Production

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jul 11

PMID 38992199

Authors

Eugenia Licari

Giulia Cricri

Mario Mauri

Francesca Raimondo

Laura Dioni

Chiara Favero

Alice Giussani

Rita Starace

Silvia Nucera

Andrea Biondi

Rocco Piazza

Valentina Bollati

Erica Dander

Giovanna DAmico

Affiliations

Soon will be listed here.

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.

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