RNA trafficking by acute myelogenous leukemia exosomes

Jianya Huan, Noah I. Hornick, Matthew J. Shurtleff, Amy M. Skinner, Natalya A. Goloviznina, Charles T. Roberts, Peter Kurre

    Research output: Contribution to journalArticlepeer-review

    148 Scopus citations

    Abstract

    Extrinsic signaling cues in the microenvironment of acute myelogenous leukemia (AML) contribute to disease progression and therapy resistance. Yet, it remains unknown how the bone marrow niche in which 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 noncoding RNAs relevant to AML pathogenesis. Furthermore, their uptake by bone marrow stromal cells altered their secretion of growth factors. Proof-ofconcept 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 cocultured stromal and hematopoietic progenitor cell lines, helping explain how the microenvironmental niche becomes reprogrammed during invasion of the bone marrow by AML.

    Original languageEnglish (US)
    Pages (from-to)918-929
    Number of pages12
    JournalCancer Research
    Volume73
    Issue number2
    DOIs
    StatePublished - Jan 15 2013

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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