Nehrbas Jill, Butler John T, Chen Ding-Wen, Kurre Peter
Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, PA, United States.
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Front Oncol. 2020 Feb 14;10:90. doi: 10.3389/fonc.2020.00090. eCollection 2020.
Extracellular vesicle (EV) trafficking provides for a constitutive mode of cell-cell communication within tissues and between organ systems. Different EV subtypes have been identified that transfer regulatory molecules between cells, influencing gene expression, and altering cellular phenotypes. Evidence from a range of studies suggests that EV trafficking enhances cell survival and resistance to chemotherapy in solid tumors. In acute myeloid leukemia (AML), EVs contribute to the dynamic crosstalk between AML cells, hematopoietic elements and stromal cells and promote adaptation of compartmental bone marrow (BM) function through transport of protein, RNA, and DNA. Careful analysis of leukemia cell EV content and phenotypic outcomes provide evidence that vesicles are implicated in transferring several known key mediators of chemoresistance, including miR-155, IL-8, and BMP-2. Here, we review the current understanding of how EVs exert their influence in the AML niche, and identify research opportunities to improve outcomes for relapsed or refractory AML patients.
细胞外囊泡（EV）运输为组织内以及器官系统之间的细胞间通讯提供了一种组成性模式。已鉴定出不同的EV亚型，它们在细胞之间传递调节分子，影响基因表达并改变细胞表型。一系列研究的证据表明，EV运输可提高实体瘤中的细胞存活率和对化疗的抗性。在急性髓细胞白血病（AML）中，EV有助于AML细胞、造血成分和基质细胞之间的动态串扰，并通过蛋白质、RNA和DNA的运输促进隔室化骨髓（BM）功能的适应。对白血病细胞EV含量和表型结果的仔细分析提供了证据，表明囊泡参与转移几种已知的化疗抗性关键介质，包括miR-155、IL-8和BMP-2。在这里，我们综述了目前对EV如何在AML生态位中发挥作用的理解，并确定改善复发或难治性AML患者预后的研究机会。
