Prognostic and therapeutic significance of XPO1 in T-cell lymphoma.
Exp Cell Res
; 416(2): 113180, 2022 07 15.
Article
en En
| MEDLINE
| ID: mdl-35489384
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfoma de Células T
/
Hidrazinas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
China