Human acute myeloid leukemia blast-derived exosomes in patient-derived xenograft mice mediate immune suppression

Experimental Hematology
Chang-Sook HongMichael Boyiadzis

Abstract

Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes originate from leukemic blasts or from various normal cells in the bone marrow or other tissues is unknown. In the current study, we developed an AML PDX model in mice and studied the molecular cargo and immune cell effects of the AML PDX exosomes in parallel with the exosomes from plasma of the corresponding AML patients. Fully engrafted AML PDX mice produced exosomes with characteristics similar to those of exosomes isolated from plasma of the AML patients who had donated the cells for engraftment. The engrafted leukemic cells produced exosomes that carried human proteins and leukemia-associated antigens, confirming the human origin of these exosomes. Furthermore, the AML-derived exosomes carried immunosuppressive proteins responsible for immune cell dysfunctions. Our studies of exosomes in AML PDX mice serve as a proof of concept that AML blasts are the source of immunosuppressive exosomes with a molecular profile th...Continue Reading

Citations

Nov 30, 2019·British Journal of Haematology·A John Barrett
Aug 20, 2020·Expert Opinion on Biological Therapy·Malgorzata Czystowska-Kuzmicz, Theresa L Whiteside
Sep 11, 2020·The FEBS Journal·Fernanda G Kugeratski, Raghu Kalluri
Jun 24, 2020·International Journal of Molecular Sciences·Eliane Ebnoether, Laurent Muller
Oct 19, 2019·Molecular Aspects of Medicine·Nithya MudgapalliKishore B Challagundla
Jan 14, 2021·Non-coding RNA·Heidi Schwarzenbach, Peter B Gahan
Oct 30, 2020·International Journal of Nanomedicine·Victor C Kok, Cheng-Chia Yu
Apr 4, 2021·Cancers·Julian SwatlerKatarzyna Piwocka

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