ANGPTL2-Containing Exosomes from Vascular Endothelial Cells Promote Leukemia Development

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.