文章：

来自成人T细胞白血病/淋巴瘤患者的原代细胞依赖HTLV-1 Tax蛋白表达实现NF-κB激活与存活

Primary cells from patients with adult T cell leukemia/lymphoma depend on HTLV-1 Tax expression for NF-κB activation and survival

原文发布日期：2023-05-03

DOI: 10.1038/s41408-023-00841-7

类型: Article

开放获取: 是

英文摘要：

Adult T cell leukemia/lymphoma (ATL) is an aggressive malignancy secondary to chronic infection with human T cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax initiates T cell transformation through activation of critical cellular pathways, including NF-κB. Unexpectedly, Tax protein is not detectable in most ATL cells, in contrast to the HTLV-1 HBZ protein which antagonizes Tax effects. Here, we demonstrate that primary ATL cells from patients with acute or chronic ATL express very low levels of Tax mRNA and protein. Critically, survival of these primary ATL cells is dependent on continued Tax expression. Mechanistically, Tax extinction results in reversal of NF-κB activation, P53/PML activation and apoptosis. Tax drives interleukin-10 (IL-10) expression and recombinant IL-10 rescues the survival of tax-depleted primary ATL cells. These results demonstrate the critical role of continued Tax and IL-10 expression for the survival of primary ATL cells, highlighting their relevance as therapeutic targets.
 

摘要翻译： 

成人T细胞白血病/淋巴瘤（ATL）是一种由人类T细胞白血病病毒1型（HTLV-1）慢性感染引发的侵袭性恶性肿瘤。病毒癌蛋白Tax通过激活NF-κB等关键细胞通路启动T细胞转化。值得注意的是，与HTLV-1中拮抗Tax效应的HBZ蛋白不同，大多数ATL细胞中检测不到Tax蛋白。本研究证实，急性或慢性ATL患者体内的原代ATL细胞仅表达极低水平的Tax mRNA与蛋白。关键在于，这些原代ATL细胞的生存依赖Tax的持续表达。从机制上看，Tax表达终止会导致NF-κB活化逆转、P53/PML激活并引发细胞凋亡。Tax可驱动白细胞介素-10（IL-10）表达，而重组IL-10能挽救Tax缺失的原代ATL细胞的生存。这些结果揭示了持续表达的Tax与IL-10对原代ATL细胞存活的关键作用，提示其作为治疗靶点的重要性。

原文链接：

Primary cells from patients with adult T cell leukemia/lymphoma depend on HTLV-1 Tax expression for NF-κB activation and survival