Bortezomib induces cell apoptosis and increases the efficacy of αPD-1 in BCR::ABL T315I mutation CML by targeting UBE2Q1.

Autor: Jiang F; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Liu W; Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, PR China., Zhou Y; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Lin S; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Zhang Q; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Zhang W; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Xue Y; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Li C; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Gao A; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Shao M; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Liao S; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Ma T; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China., Yu X; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, PR China. Electronic address: xxyu@njucm.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Dec 25; Vol. 143 (Pt 2), pp. 113311. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.intimp.2024.113311
Abstrakt: The BCR:ABL T315I mutation presents a significant challenge in the current management of Chronic Myeloid Leukemia (CML), highlighting the need to identify novel targets and drugs. In our study, we observed the elevated expression of UBE2Q1 in KBM5-T315I cells compared to KBM5 cells, where it interacted with DDX3, regulating its ubiquitination. Furthermore, we found that Bortezomib (BTZ) targeted UBE2Q1, reducing its protein level expression. Consequently, BTZ dose-dependently inhibited the growth vitality of KBM5-T315I cells, inducing increased ROS production, mitochondrial membrane potential collapse, cytochrome C release, and expression of apoptosis-related proteins. These events collectively induced apoptosis in KBM5-T315I cells. Moreover, BTZ enhanced the therapeutic effects of anti-PD-1 treatment. In NOD/SCID mice bearing KBM5-T315I cell line xenografts, BTZ administration (2 mg/kg, ip, every other day for 4 weeks) significantly inhibited the growth of KBM5-T315Iderived xenografts and extended survival. In conclusion, our study sheds new light on the BTZ-induced apoptosis mechanism, suggesting the potential of BTZ as a promising chemo-immunotherapy agent against BCR:ABL T315I mutation CML.
Competing Interests: Declaration of competing interest 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.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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