Combined Inhibition of XPO1 and DNA Methylation Exerts Synergistic Effects in DLBCL
Qi Li
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXiaofeng Xue
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorSi Chen
Suzhou Sano Precision Medicine Ltd., Suzhou, Jiangsu, China
Search for more papers by this authorXinyun Zhang
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorYuchen Zhang
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorRuijing Hu
Suzhou Sano Precision Medicine Ltd., Suzhou, Jiangsu, China
Search for more papers by this authorXinyuan Zhang
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorLinlin Qin
Suzhou Sano Precision Medicine Ltd., Suzhou, Jiangsu, China
Search for more papers by this authorMenglu Chen
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Wenzhuo Zhuang
Department of Cell Biology, School of Basic Medical Sciences, Soochow University, Suzhou, Jiangsu, China
Correspondence: Wenzhuo Zhuang ([email protected])
Bingzong Li ([email protected])
Search for more papers by this authorCorresponding Author
Bingzong Li
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Correspondence: Wenzhuo Zhuang ([email protected])
Bingzong Li ([email protected])
Search for more papers by this authorQi Li
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorXiaofeng Xue
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorSi Chen
Suzhou Sano Precision Medicine Ltd., Suzhou, Jiangsu, China
Search for more papers by this authorXinyun Zhang
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorYuchen Zhang
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorRuijing Hu
Suzhou Sano Precision Medicine Ltd., Suzhou, Jiangsu, China
Search for more papers by this authorXinyuan Zhang
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorLinlin Qin
Suzhou Sano Precision Medicine Ltd., Suzhou, Jiangsu, China
Search for more papers by this authorMenglu Chen
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Wenzhuo Zhuang
Department of Cell Biology, School of Basic Medical Sciences, Soochow University, Suzhou, Jiangsu, China
Correspondence: Wenzhuo Zhuang ([email protected])
Bingzong Li ([email protected])
Search for more papers by this authorCorresponding Author
Bingzong Li
Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
Correspondence: Wenzhuo Zhuang ([email protected])
Bingzong Li ([email protected])
Search for more papers by this authorQi Li and Xiaofeng Xue contributed equally to this study.
ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma characterized by high rates of relapse and limited responsiveness to standard chemotherapy. Selinxor, a selective inhibitor of XPO1, exhibited antitumor activity in various cancers. However, clinical trial results revealed that selinexor monotherapy exhibited unsatisfactory efficacy in DLBCL. Our study indicated that XPO1 expression was increased in DLBCL and was correlated with poor outcomes of DLBCL patients. Comprehensive proteomic and transcriptomics analysis showed that selinexor has significant impacts on various biological processes in DLBCL. Furthermore, we explored combination strategies involving selinexor to enhance DLBCL treatment. We examined the combined effects of selinexor with decitabine (DAC) and lenalidomide (LEN), and found that selinexor exhibited a synergistic effect with DAC against DLBCL. Further analysis revealed that DAC exerted a synergistic antitumor effect with selinexor by reversing the DNMT1 expression and DNA methylation alterations induced by selinexor. Overall, these findings provided valuable insights into the global impact of selinexor on DLBCL. The combination therapy of selinexor and DAC emerges as a highly promising strategy for effectively treating DLBCL, holding great potential for clinical application.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
The TCGA DLBC cohort data was obtained from TCGA data portal (https://tcga-data.nci.nih.gov/tcga). Public microarray data, including clinical information, were downloaded from the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/), with the accession number GSE10846. The raw sequencing data relevant to this study have also been uploaded to GEO under the accession number GSE294167. Additional data supporting the findings of this study are available within the article or can be obtained from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
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| mc70014-sup-0001-supplementary_material.docx1.7 MB | supplementary material. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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