Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-City, Mie 514-8507, Japan.
Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu-City, Mie 514-8507, Japan.
Int J Mol Sci. 2021 Feb 13;22(4):1881. doi: 10.3390/ijms22041881.
Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.
白血病是一种起源于骨髓造血干细胞的血液系统恶性肿瘤。人们在理解其发病机制以及建立化疗和造血干细胞移植治疗(HSCT)方面取得了重大进展。然而,尽管新的治疗方法,如分子靶向治疗和免疫治疗,不断发展,一些患者仍然无法被治愈,并且治疗耐药和复发仍然是白血病患者需要解决的问题。骨髓(BM)龛是一个包含造血干细胞及其支持细胞的微环境。白血病细胞与骨髓龛相互作用并调节它们,不仅诱导分子和功能变化,而且还转向白血病细胞偏好的龛。后者与白血病进展、正常造血抑制和化疗耐药密切相关,这正是正在研究的领域。外泌体在细胞间通讯中起着重要作用,不仅与邻近细胞,而且与由于外泌体通过体液循环而更远处的细胞进行通讯。在白血病中,外泌体在白血病发生、疾病进展和器官侵袭中发挥重要作用,并且最近已经报道了它们在白血病诊断和治疗中的用途。白血病细胞衍生的外泌体与 BM 微环境之间的相互作用受到了特别关注。它们的相互作用被认为起着非常重要的作用;除了具有诊断价值外,外泌体还可以作为监测治疗效果的标志物,并有助于克服白血病患者尚未克服的许多问题中的药物耐药性。在本文中,我们将综述白血病中的骨髓龛、白血病衍生的外泌体的研究发现,以及外泌体诱导的骨髓龛变化。