Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Expert Opin Ther Targets. 2020 May;24(5):451-462. doi: 10.1080/14728222.2020.1744850. Epub 2020 Mar 26.
: Myeloid malignancies are caused by uncontrolled proliferation of neoplastic cells and lack of mature hematopoietic cells. Beside intrinsic genetic and epigenetic alterations within the neoplastic population, abnormal function of the bone marrow stroma promotes the neoplastic process. To overcome the supportive action of the microenvironment, recent research focuses on the development of targeted therapies, inhibiting the interaction of malignant cells and niche cells.: This review covers regulatory networks and potential druggable pathways within the hematopoietic stem cell niche. Recent insights into the cell-to-cell interactions in the bone marrow microenvironment are presented. We performed literature searches using PubMed Database from 2000 to the present.: Future therapy of myeloid malignancies must focus on targeted, personalized treatment addressing specific alterations within the malignant and the supporting niche cells. This includes treatments to overcome resistance mechanisms against chemotherapeutic agents mediated by supporting microenvironment. Novel techniques employing sequencing approaches, Crisp/Cas9, or transgenic mouse models are required to elucidate specific interactions between components of the bone marrow niche to identify new therapeutic targets.
髓系恶性肿瘤是由肿瘤细胞的失控增殖和缺乏成熟造血细胞引起的。除了肿瘤群体内部的内在遗传和表观遗传改变外,骨髓基质的异常功能也促进了肿瘤的发生。为了克服微环境的支持作用,最近的研究集中在开发靶向治疗上,抑制恶性细胞和龛细胞的相互作用。
这篇综述涵盖了造血干细胞龛内的调节网络和潜在的可药物治疗途径。本文介绍了骨髓微环境中细胞间相互作用的最新见解。我们使用 PubMed 数据库从 2000 年到现在进行了文献检索。
髓系恶性肿瘤的未来治疗必须集中在针对恶性和支持龛细胞内特定改变的靶向、个性化治疗上。这包括针对由支持微环境介导的化疗药物耐药机制的治疗。需要采用测序方法、Crisp/Cas9 或转基因小鼠模型等新技术来阐明骨髓龛中成分之间的特定相互作用,以确定新的治疗靶点。