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926 ANGPTL2-Containing Exosomes from Vascular Endothelial Cells Promote Leukemia Development

Program: Oral and Poster Abstracts
Session: 506. Hematopoiesis and Stem Cells: Microenvironment, Cell Adhesion, and Stromal Stem Cells: Poster I
Hematology Disease Topics & Pathways:
Diseases, Biological Processes, microenvironment
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Guohuan Sun1*, Dan Huang2*, Xiaoxin Hao2*, Xiaoxiao He2*, Zhaofeng Zheng1*, Chiqi Chen2*, Zhuo Yu2*, Li Xie2*, Shihui Ma, MD1*, Ligen Liu2, Bo Zhou3*, Hui Cheng1*, Junke Zheng2* and Tao Cheng4

1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
2Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education; Shanghai Jiao Tong University School of Medicine; State Key Laboratory of Experimental Hematolo, Shanghai, China
3State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
4State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China

Exosomes are functional messengers of certain cellular niches to permit non-contact cell communications. Whether niche-specific exosomes fulfill this role in cancer is unclear. Here, we show that blocking exosome secretion from endothelial cells (ECs), but not perivascular cells, megakaryocytes or spleen stromal cells, markedly delayed the progression of acute myeloid leukemia (AML). Notably, reducing exosome production from ECs had no effect on normal hematopoiesis. EC-derived exosomes contained a high level of ANGPTL2, which supported AML development via binding to LILRB2 receptor. Moreover, ANGPTL2 exosome released from ECs was governed by VPS33B. These findings demonstrate a role of niche-specific exosomes in cancer development and suggest that targeting ANGPTL2 exosomes from ECs might be a potential strategy to interfere AML.

Disclosures: No relevant conflicts of interest to declare.

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