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Transferred BCR/ABL DNA from K562 extracellular vesicles causes chronic myeloid leukemia in immunodeficient mice.

Authors: Cai, Jin  Wu, Gengze  Tan, Xiaorong  Han, Yu  Chen, Caiyu  Li, Chuanwei  Wang, Na  Zou, Xue  Chen, Xinjian  Zhou, Faying  He, Duofen  Zhou, Lin  Jose, Pedro A  Zeng, Chunyu 
Citation: Cai J, etal., PLoS One. 2014 Aug 18;9(8):e105200. doi: 10.1371/journal.pone.0105200. eCollection 2014.
Pubmed: (View Article at PubMed) PMID:25133686
DOI: Full-text: DOI:10.1371/journal.pone.0105200

Our previous study showed that besides mRNAs and microRNAs, there are DNA fragments within extracellular vesicles (EVs). The BCR/ABL hybrid gene, involved in the pathogenesis of chronic myeloid leukemia (CML), could be transferred from K562 EVs to neutrophils and decrease their phagocytic activity in vitro. Our present study provides evidence that BCR/ABL DNAs transferred from EVs have pathophysiological significance in vivo. Two months after injection of K562 EVs into the tail vein of Sprague-Dawley (SD) rats, they showed some characteristics of CML, e.g., feeble, febrile, and thin, with splenomegaly and neutrophilia but with reduced neutrophil phagocytic activity. These findings were also observed in immunodeficient NOD/SCID mice treated with K562 EVs; BCR/ABL mRNA and protein were found in their neutrophils. The administration of actinomycin D, an inhibitor of de novo mRNA synthesis, prevented the abnormalities caused by K562 EVs in NOD/SCID mice related to CML, including neutrophilia and bone marrow hyperplasia. As a specific inhibitor of tyrosine kinases, imatinib blocked the activity of tyrosine kinases and the expression of phospho-Crkl, induced by the de novo BCR/ABL protein caused by K562 EVs bearing BCR/ABL DNA. Our current study shows the pathophysiological significance of transferred tumor gene from EVs in vivo, which may represent an important mechanism for tumorigenesis, tumor progression, and metastasis.

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CRRD Object Information
CRRD ID: 13674161
Created: 2018-07-10
Species: All species
Last Modified: 2018-07-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.