Fiche publication
Date publication
avril 2022
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen
,
Dr PAIS DE BARROS Jean-Paul
,
Dr QUERE Ronan
Tous les auteurs :
Georgievski A, Michel A, Thomas C, Mlamla Z, Pais de Barros JP, Lemaire-Ewing S, Garrido C, Quéré R
Lien Pubmed
Résumé
Patient-derived xenografted (PDX) models were generated through the transplantation of primary acute lymphoblastic leukemia (ALL) cells into immunodeficient NSG mice. We observed that ALL cells from mouse bone marrow (BM) produced extracellular vesicles (EVs) with specific expression of inducible heat shock protein HSP70, which is commonly activated in cancer cells. Taking advantage of this specific expression, we designed a strategy to generate fluorescent HSP70-labeled ALL EVs and monitor the impact of these EVs on endogenous murine BM cells ex vivo and in vivo. We discovered that hematopoietic stem and progenitor cells (HSPC) were mainly targeted by ALL EVs, affecting their quiescence and maintenance in the murine BM environment. Investigations revealed that ALL EVs were enriched in cholesterol and other metabolites that contribute to promote the mitochondrial function in targeted HSPC. Furthermore, using CD34 cells isolated from cord blood, we confirmed that ALL EVs can modify quiescence of human HSPC. In conclusion, we have discovered a new oncogenic mechanism illustrating how EVs produced by proliferative ALL cells can target and compromise a healthy hematopoiesis system during leukemia development.
Mots clés
Animals, Extracellular Vesicles, metabolism, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, metabolism, Mice, Precursor Cell Lymphoblastic Leukemia-Lymphoma, genetics
Référence
Cell Death Dis. 2022 Apr 12;13(4):337
