Prognostic and therapeutic significance of XPO1 in T-cell lymphoma.

Danian Nie, Xiaohui Xiao, Jiaoting Chen, Shuangfeng Xie, Jie Xiao, Wenjuan Yang, Hongyun Liu, Jieyu Wang, Liping Ma, Yumo Du, Kezhi Huang, Yiqing Li

Experimental cell research 2022 Jul 15

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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 vitro treatment 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. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Danian Nie, Xiaohui Xiao, Jiaoting Chen, Shuangfeng Xie, Jie Xiao, Wenjuan Yang, Hongyun Liu, Jieyu Wang, Liping Ma, Yumo Du, Kezhi Huang, Yiqing Li. Prognostic and therapeutic significance of XPO1 in T-cell lymphoma. Experimental cell research. 2022 Jul 15;416(2):113180