Satou Yorifumi, Matsuoka Masao
Laboratory for Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Int J Hematol. 2007 Aug;86(2):107-12. doi: 10.1532/IJH97.07103.
Adult T-cell leukemia (ATL) is a leukemia derived from CD4+ mature T-cells and induced by human T-cell leukemia virus type I (HTLV-I) infection. Although previous studies have revealed many aspects of its leukemogenesis, enigmas remain about how HTLV-I transforms mature T-cells in infected individuals. Furthermore, an effective therapy for ATL has not yet been established. The critical role of a nonstructural regulatory viral protein, Tax, in transformation has been established through many molecular studies, in vitro cell culture experiments, and transgenic mouse model systems. In addition, other accessory viral proteins have been implicated in ATL pathogenesis. Recent studies of a minus strand viral gene, HTLV-I bZIP factor (HBZ), suggest it plays a role in ATL leukemogenesis. In addition to viral components, genetic and epigenetic events of the host cellular genome must be considered in developing a complete picture of the transformation process. In this review, we summarize the molecular and cellular mechanisms involved in the leukemogenesis induced by HTLV-I; we consider both viral and host cellular factors and focus particularly on the viral gene HBZ.
成人T细胞白血病（ATL）是一种源自CD4 +成熟T细胞并由I型人类T细胞白血病病毒（HTLV-I）感染诱导产生的白血病。尽管先前的研究已经揭示了其白血病发生的许多方面，但关于HTLV-I如何在受感染个体中转化成熟T细胞仍存在谜团。此外，尚未建立针对ATL的有效治疗方法。通过许多分子研究、体外细胞培养实验和转基因小鼠模型系统，已确定非结构调节病毒蛋白Tax在转化中起关键作用。此外，其他辅助病毒蛋白也与ATL发病机制有关。最近对负链病毒基因HTLV-I bZIP因子（HBZ）的研究表明，它在ATL白血病发生中起作用。除了病毒成分外，在全面了解转化过程时，还必须考虑宿主细胞基因组的遗传和表观遗传事件。在本综述中，我们总结了HTLV-I诱导白血病发生所涉及的分子和细胞机制；我们考虑了病毒和宿主细胞因素，并特别关注病毒基因HBZ。
