RNA trafficking by acute myelogenous leukemia exosomes

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

Research output: Contribution to journalArticle

115 Citations (Scopus)

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

Fingerprint

Exosomes
Acute Myeloid Leukemia
RNA
Bone Marrow
Cell Line
Untranslated RNA
Hematopoietic Stem Cells
Mesenchymal Stromal Cells
Cell Communication
Cues
Disease Progression
Intercellular Signaling Peptides and Proteins
Cell Membrane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Huan, J., Hornick, N. I., Shurtleff, M. J., Skinner, A., Goloviznina, N. A., Roberts, C., & Kurre, P. (2013). RNA trafficking by acute myelogenous leukemia exosomes. Cancer Research, 73(2), 918-929. https://doi.org/10.1158/0008-5472.CAN-12-2184

RNA trafficking by acute myelogenous leukemia exosomes. / Huan, Jianya; Hornick, Noah I.; Shurtleff, Matthew J.; Skinner, Amy; Goloviznina, Natalya A.; Roberts, Charles; Kurre, Peter.

In: Cancer Research, Vol. 73, No. 2, 15.01.2013, p. 918-929.

Research output: Contribution to journalArticle

Huan, J, Hornick, NI, Shurtleff, MJ, Skinner, A, Goloviznina, NA, Roberts, C & Kurre, P 2013, 'RNA trafficking by acute myelogenous leukemia exosomes', Cancer Research, vol. 73, no. 2, pp. 918-929. https://doi.org/10.1158/0008-5472.CAN-12-2184
Huan J, Hornick NI, Shurtleff MJ, Skinner A, Goloviznina NA, Roberts C et al. RNA trafficking by acute myelogenous leukemia exosomes. Cancer Research. 2013 Jan 15;73(2):918-929. https://doi.org/10.1158/0008-5472.CAN-12-2184
Huan, Jianya ; Hornick, Noah I. ; Shurtleff, Matthew J. ; Skinner, Amy ; Goloviznina, Natalya A. ; Roberts, Charles ; Kurre, Peter. / RNA trafficking by acute myelogenous leukemia exosomes. In: Cancer Research. 2013 ; Vol. 73, No. 2. pp. 918-929.
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