Extracellular Vesicles Impose Quiescence on Residual Hematopoietic Stem Cells in the Leukemic Niche

ABSTRACT: Progressive remodeling of the bone marrow microenvironment is recognized as an integral aspect of leukemogenesis. Expanding Acute myeloid Leukemia (AML) clones not only alter stroma composition, but actively constrain hematopoiesis, representing a significant source of patient morbidity and mortality. Recent studies revealed the surprising resistance of long-term hematopoietic stem cells (LT-HSC) to elimination from the leukemic niche. Here we examine the fate and function of residual LT-HSC in the BM of murine xenografts with emphasis on the role of AML-derived Extracellular Vesicles (EV). AML-EV rapidly enter HSC and their trafficking elicits protein synthesis suppression and LT-HSC quiescence. Mechanistically, AML-EV transfer a panel of miRNA, including miR-1246, that target the mTOR su

SUBMITTER: Dr. Sherif Abdelhamed 

PROVIDER: S-SCDT-EMBOR-2018-47546-T | biostudies-other |

REPOSITORIES: biostudies-other