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Tumor and Stem Cell Biology

RNA Trafficking by Acute Myelogenous Leukemia Exosomes

Jianya Huan, Noah I. Hornick, Matthew J. Shurtleff, Amy M. Skinner, Natalya A. Goloviznina, Charles T. Roberts Jr and Peter Kurre
Jianya Huan
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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Noah I. Hornick
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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Matthew J. Shurtleff
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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Amy M. Skinner
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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Natalya A. Goloviznina
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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Charles T. Roberts
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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Peter Kurre
Authors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, OregonAuthors' Affiliations: Departments of Pediatrics, Cell & Developmental Biology, and Medicine; Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland; and Oregon National Primate Research Center, Beaverton, Oregon
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DOI: 10.1158/0008-5472.CAN-12-2184 Published January 2013
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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-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 cocultured stromal and hematopoietic progenitor cell lines, helping explain how the microenvironmental niche becomes reprogrammed during invasion of the bone marrow by AML. Cancer Res; 73(2); 918–29. ©2012 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Prior presentation: This work was presented, in part, at the 2011 meeting of the American Society of Hematology.

  • Received May 31, 2012.
  • Revision received October 12, 2012.
  • Accepted November 5, 2012.
  • ©2012 American Association for Cancer Research.
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Cancer Research: 73 (2)
January 2013
Volume 73, Issue 2
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RNA Trafficking by Acute Myelogenous Leukemia Exosomes
Jianya Huan, Noah I. Hornick, Matthew J. Shurtleff, Amy M. Skinner, Natalya A. Goloviznina, Charles T. Roberts Jr and Peter Kurre
Cancer Res January 15 2013 (73) (2) 918-929; DOI: 10.1158/0008-5472.CAN-12-2184

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RNA Trafficking by Acute Myelogenous Leukemia Exosomes
Jianya Huan, Noah I. Hornick, Matthew J. Shurtleff, Amy M. Skinner, Natalya A. Goloviznina, Charles T. Roberts Jr and Peter Kurre
Cancer Res January 15 2013 (73) (2) 918-929; DOI: 10.1158/0008-5472.CAN-12-2184
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