Division of Hematology-Oncology, Departments of Medicine.
Pathology, Immunology and Otolaryngology, University of Pittsburgh, Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
Curr Opin Hematol. 2018 Jul;25(4):279-284. doi: 10.1097/MOH.0000000000000439.
Exosomes are cell-derived, biologically active membrane-bound vesicles, and are emerging as key modulators of hematopoiesis. Recent studies have provided a clearer understanding of the mechanisms whereby blast-derived exosomes act to suppress hematopoiesis in acute myeloid leukemia (AML).
Exosomes released from leukemia blasts have been shown to suppress hematopoietic progenitor cell (HPC) functions indirectly through stromal reprogramming of niche-retention factors and also as a consequence of AML exosome-directed microRNA delivery to HPC. Furthermore, exosomes secreted by AML blasts remodel the bone marrow niche into a leukemia growth-permissive microenvironment.
Exosomes suppress hematopoiesis in AML. Strategies to block the production, secretion and reprogramming that exosomes induce may be a novel therapeutic approach in AML and other leukemias.
外泌体是由细胞衍生的、具有生物活性的膜结合囊泡,正在成为造血的关键调节因子。最近的研究提供了更清晰的认识,即胚细胞来源的外泌体如何抑制急性髓细胞白血病(AML)中的造血。
已经证明,白血病细胞释放的外泌体通过基质重编程龛保留因子间接抑制造血祖细胞(HPC)的功能,并且还由于 AML 外泌体指导的 microRNA 递送到 HPC。此外,AML 胚细胞分泌的外泌体重塑骨髓龛为白血病生长许可的微环境。
外泌体抑制 AML 中的造血。阻断外泌体产生、分泌和诱导的重编程的策略可能是 AML 和其他白血病的一种新的治疗方法。