Division of Oncology, Washington University School of Medicine, Box 8069, 660 S Euclid Ave, St Louis, MO 63110, United States.
Semin Diagn Pathol. 2020 Mar;37(2):104-109. doi: 10.1053/j.semdp.2019.04.003. Epub 2019 Apr 16.
Human T cell leukemia virus type 1 (HTLV-1) is a horizontally transmitted virus infection of CD4+ lymphocytes which causes adult T cell leukemia-lymphoma (ATLL) and HTLV-associated myelopathy (HAM). The viral genome encodes two oncoproteins, transactivator protein (Tax) and helix basic zipper protein (HBZ), which are considered tumor initiator and maintenance factors, respectively. Tax is the primary inducer of clonal infected T cell expansion, and genetic instability. The immune response to Tax results in the selection of cells with little or no Tax expression, which have undergone genetic and epigenetic alterations that promote T cell activation, proliferation, and resistance to apoptosis. This selection of malignant cells occurs over several decades in 5% of infected individuals. Novel insights into the molecular details of each of these events has led to targeted therapies for ATLL.
人类 T 细胞白血病病毒 1 型（HTLV-1）是一种水平传播的 CD4+淋巴细胞病毒感染，可导致成人 T 细胞白血病-淋巴瘤（ATLL）和 HTLV 相关脊髓病（HAM）。病毒基因组编码两种致癌蛋白，即反式激活蛋白（Tax）和螺旋碱性拉链蛋白（HBZ），它们分别被认为是肿瘤启动子和维持因子。Tax 是克隆感染 T 细胞扩增和遗传不稳定性的主要诱导物。对 Tax 的免疫反应导致选择表达少量或无 Tax 的细胞，这些细胞经历了促进 T 细胞激活、增殖和抗凋亡的遗传和表观遗传改变。在感染个体中，这种恶性细胞的选择发生在几十年内，比例为 5%。对这些事件的分子细节的新见解导致了针对 ATLL 的靶向治疗。
