Moodad Sara, Akkouche Abdou, Hleihel Rita, Darwiche Nadine, El-Sabban Marwan, Bazarbachi Ali, El Hajj Hiba
Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Front Microbiol. 2018 Mar 28;9:558. doi: 10.3389/fmicb.2018.00558. eCollection 2018.
Adult T cell Leukemia (ATL) is an aggressive lymphoproliferative malignancy secondary to infection by the human T-cell leukemia virus type I (HTLV-I) and is associated with a dismal prognosis. ATL leukemogenesis remains enigmatic. In the era of precision medicine in oncology, mouse models offer one of the most efficient tools for the understanding of the disease biology and developing novel targeted therapies. This review provides an up-to-date and comprehensive account of mouse models developed in the context of ATL and HTLV-I infection. Murine ATL models include transgenic animals for the viral proteins Tax and HBZ, knock-outs for key cellular regulators, xenografts and humanized immune-deficient mice. The first two groups provide a key understanding of the role of viral and host genes in the development of ATL, as well as their relationship with the immunopathogenic processes. The third group represents a valuable platform to test new targeted therapies against ATL.
成人T细胞白血病(ATL)是一种侵袭性淋巴细胞增殖性恶性肿瘤,继发于人类T细胞白血病病毒I型(HTLV-I)感染,预后不佳。ATL的白血病发生机制仍然不明。在肿瘤学精准医学时代,小鼠模型是理解疾病生物学和开发新型靶向治疗方法最有效的工具之一。本综述提供了在ATL和HTLV-I感染背景下开发的小鼠模型的最新全面介绍。鼠类ATL模型包括表达病毒蛋白Tax和HBZ的转基因动物、关键细胞调节因子的基因敲除动物、异种移植模型和人源化免疫缺陷小鼠。前两组有助于深入了解病毒和宿主基因在ATL发生发展中的作用,以及它们与免疫致病过程的关系。第三组是测试针对ATL的新靶向治疗方法的宝贵平台。