斑马鱼异种移植模型中白血病-生态位相互作用的体内监测。
In vivo monitoring of leukemia-niche interactions in a zebrafish xenograft model.
发表日期:2024
作者:
Anja Arner, Andreas Ettinger, Bradley Wayne Blaser, Bettina Schmid, Irmela Jeremias, Nadia Rostam, Vera Binder-Blaser
来源:
Experimental Hematology & Oncology
摘要:
急性淋巴细胞白血病(ALL)是儿童最常见的恶性肿瘤类型。初步诊断后 ALL 的预后通常良好;然而,复发的患者预后不佳。肿瘤微环境被认为是复发的重要因素,但所涉及的细胞间相互作用非常复杂,难以在传统实验模型中研究。在本研究中,我们建立了一种创新的幼虫斑马鱼异种移植模型,该模型允许使用延时显微镜和流式细胞术方法分析原位生态位内的白血病细胞(LC)。移植时,LC 在造血生态位(尾部造血组织 (CHT))内归巢、移植并增殖。记录了 CHT 内 LC 的特定传播模式,因为它们随着时间的推移外渗并形成靠近背主动脉的簇。可以定量表征LC与巨噬细胞和内皮细胞的相互作用。该斑马鱼模型将允许在功能性和复杂的微环境中对 LC 进行定量分析,以研究生态位介导的白血病发生、白血病维持和复发发展的机制。版权所有:© 2024 Arner 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章,允许在任何媒体上不受限制地使用、分发和复制,前提是注明原始作者和来源。
Acute lymphoblastic leukemia (ALL) is the most common type of malignancy in children. ALL prognosis after initial diagnosis is generally good; however, patients suffering from relapse have a poor outcome. The tumor microenvironment is recognized as an important contributor to relapse, yet the cell-cell interactions involved are complex and difficult to study in traditional experimental models. In the present study, we established an innovative larval zebrafish xenotransplantation model, that allows the analysis of leukemic cells (LCs) within an orthotopic niche using time-lapse microscopic and flow cytometric approaches. LCs homed, engrafted and proliferated within the hematopoietic niche at the time of transplant, the caudal hematopoietic tissue (CHT). A specific dissemination pattern of LCs within the CHT was recorded, as they extravasated over time and formed clusters close to the dorsal aorta. Interactions of LCs with macrophages and endothelial cells could be quantitatively characterized. This zebrafish model will allow the quantitative analysis of LCs in a functional and complex microenvironment, to study mechanisms of niche mediated leukemogenesis, leukemia maintenance and relapse development.Copyright: © 2024 Arner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.