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RNA trafficking by acute myeloid leukemia exosomes.
MedLine Citation:
PMID:  23149911     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Extrinsic signaling cues in the microenvironment of acute myeloid leukemia (AML) contribute to disease progression and therapy resistance. Yet it remains unknown how the bone marrow niche where AML arises is subverted to support leukemic persistence at the expense of homeostatic function. Exosomes are cell membrane-derived vesicles carrying protein and RNA cargoes that have emerged as mediators of cell-cell communication. In this study, we examined the role of exosomes in developing the AML niche of the bone marrow microenvironment, investigating their biogenesis with a focus on RNA trafficking. We found that both primary AML and AML cell lines released exosome-sized vesicles that entered bystander cells. These exosomes were enriched for several coding- and non-coding RNAs relevant to AML pathogenesis. Further, their uptake by bone marrow stromal cells altered their secretion of growth factors. Proof-of-concept studies provided additional evidence for the canonical functions of the transferred RNA. Taken together, our findings revealed that AML exosome trafficking alters the proliferative, angiogenic, and migratory responses of co-cultured stromal and hematopoietic progenitor cell lines, helping explain how the microenvironmental niche becomes reprogrammed during invasion of the bone marrow by AML.
Authors:
Jianya Huan; Noah I Hornick; Amy M Skinner; Natalya A Goloviznina; Charles T Roberts; Peter Kurre
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Cancer research     Volume:  -     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Pediatrics, Oregon Health & Science University.
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