Prognostic and therapeutic significance of XPO1 in T-cell lymphoma
Prognostic and therapeutic significance of XPO1 in T-cell lymphoma
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XPO1 在 T 细胞淋巴瘤中的预后和治疗意义
DOI：
10.1016/j.yexcr.2022.113180
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发表时间：
2022
影响因子：
3.7
通讯作者：
Yiqing Li
中科院分区：
文献类型：
--
作者：
Danian Nie;Xiaohui Xiao;Jiaoting Chen;Shuangfeng Xie;Jie Xiao;Wenjuan Yang;Hongyun Liu;Jieyu Wang;Liping Ma;Yumo Du;Kezhi Huang;Yiqing Li
T细胞淋巴瘤（TCL）是一组高度异质性的侵袭性非霍奇金淋巴瘤，预后不良，治疗选择有限。TCL与主要的核输出受体Exportin-1（XPO 1）的关系尚未确定。我们在此研究XPO 1在TCL中的预后作用和治疗意义。我们分析了一组69例TCL肿瘤中XPO 1的表达，发现XPO 1在76.8%的TCL中过表达，并与无进展生存期（PFS）和总生存期（OS）降低相关。在体外，用第二代选择性核输出抑制剂（SINE）KPT-8602处理TCL细胞系，抑制XPO 1表达，并显示出显著的抗增殖作用，细胞周期停滞和促凋亡功效。在机制上，KPT-8602恢复了胞浆内FOXO 3A、p27、p21、IκBα和PP 2A的核定位，导致AKT和NF-κB失活。我们的数据首次证明XPO 1可能是TCL的不利预后因素，并为进一步研究KPT-8602在TCL患者中的疗效提供了依据。
T-cell lymphoma (TCL) is a highly heterogeneous group of invasive non-Hodgkin lymphoma with adverse prognosis and limited treatment options. The relationship between TCL and Exportin-1 (XPO1), a major nuclear export receptor, has not been established yet. We here investigated the prognostic role and therapeutic implication of XPO1 in TCL. We analyzed XPO1 expression in a cohort of 69 TCL tumors and found that XPO1 was over-expressed in 76.8% of TCL and correlated with decreased progression-free survival (PFS) and overall survival (OS).In vitrotreatment of TCL cell lines with KPT-8602, the second-generation selective inhibitor of nuclear export (SINE), inhibited XPO1 expression and showed significant anti-proliferative, cell-cycle arrest and pro-apoptotic efficacy. In mechanism, KPT-8602 restored the localization of cytoplasmic FOXO3A, p27, p21, IκBα and PP2A into the nucleus, leading to AKT and NF-κB deactivation. Our data demonstrate for the first time that XPO1 could be an unfavorable prognostic factor for TCL, and provide a rationale for further investigation of the efficacy of KPT-8602 in TCL patients.