Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Jan 24, 2024; 15(1): 115-129
Published online Jan 24, 2024. doi: 10.5306/wjco.v15.i1.115
Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma
Yang Song, Hao-Jun Zhang, Xia Song, Jie Geng, Hong-Yi Li, Li-Zhong Zhang, Bo Yang, Xue-Chun Lu
Yang Song, Hong-Yi Li, School of Basic Medicine, Medical School of Chinese PLA, Beijing 100853, China
Hao-Jun Zhang, Xia Song, Jie Geng, Li-Zhong Zhang, School of Basic Medicine, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Bo Yang, Xue-Chun Lu, Department of Hematology, The Second Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
Author contributions: Song Y and Lu XC conceived and designed the experiments. Zhang HJ, Geng J, and Song Y conducted the experiments and drafted the manuscript; Zhong LZ and Song X contributed to the techniques used and commented on the manuscript; Li HY performed the data analysis; Yang B and Lu XC assisted with revising the manuscript; All the authors reviewed the results and approved the final version of the manuscript.
Supported by the National Key Research and Development Program of China, No. 2021YFC2701704; the National Clinical Medical Research Center for Geriatric Diseases, "Multicenter RCT" Research Project, No. NCRCG-PLAGH-20230010; and the Military Logistics Independent Research Project, No. 2022HQZZ06.
Institutional review board statement: This study does not involve research on humans/animals and does not include the initial version formally approved by the Institutional Review Board in the official language of the authors' country.
Informed consent statement: This study does not involve clinical research and does not include the initial version of the informed consent form signed by all subjects and investigators.
Conflict-of-interest statement: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xue-Chun Lu, PhD, Chief Doctor, Professor, Research Scientist, Department of Hematology, The Second Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
Received: November 20, 2023
Peer-review started: November 20, 2023
First decision: December 5, 2023
Revised: December 13, 2023
Accepted: January 2, 2024
Article in press: January 2, 2024
Published online: January 24, 2024
Research background

Multiple myeloma (MM) is a terminally differentiated B-cell tumor disease with a challenging prognosis. Specifically, the t(4;14) MM is categorized as a high-risk subtype within MM.

Research motivation

The t(4;14) MM tends to relapse, and currently, there is a lack of effective clinical treatment strategies.

Research objectives

This study aimed to elucidate the molecular basis of the t(4;14) MM and search for potential effective drugs through a comprehensive approach.

Research methods

The transcriptional characteristics of t(4;14) multiple myeloma were obtained from the Gene Expression Omnibus and subjected to gene ontology and pathway enrichment analysis. Utilizing the STRING database and Cytoscape, a protein-protein interaction network was constructed, and core targets were identified. Connectivity Map identified potential small-molecule drugs, and these findings were validated through molecular docking analysis. One of these drugs, ivermectin, was further tested for its effects on t(4;14) multiple myeloma cells.

Research results

We identified 258 differentially expressed genes with enriched functions in cancer pathways, cytokine receptor interactions, the nuclear factor (NF)-kappa B signaling pathway. Ten key genes were pinpointed. Ivermectin emerged as a potential treatment. In vitro, ivermectin inhibited t(4;14) MM cell growth via the NF-kappa B pathway and induced t(4;14) MM cell apoptosis.

Research conclusions

Ivermectin induced apoptosis in t(4;14) MM cells via the NF-κB signaling pathway.

Research perspectives

Our study offers valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment.