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Published on: October 17, 2025
Bortezomib therapeutic effect is associated with expression and mutation of FGFR3 in human lymphoma cells
Weiyan Zheng1, Min Guan, Lijun Zhu
1Department of Hematology, Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang, 310003, PR China.
Objective:
Ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in many malignant cancer patients, including those with lymphoma. This study investigated whether the therapeutic effect of bortezomib in lymphoma is associated with FGFR3-expression.
Materials And Methods:
Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U937 cells and compared to U937 cells overexpressing FGFR3 wild-type, or Y373C or K650E mutant FGFR3.
Results:
Results from this study suggested the expression of FGFR3 protein is associated with the therapeutic effect of bortezomib. It was observed that bortezomib-induced apoptotic death is correlated with FGFR3 expression. U937 cells overexpression of wild-type FGFR3 demonstrated resistance to bortezomib treatment. U937 cells expressing Y373C mutated FGFR3 showed an almost equal resistance to bortezomib as U937 cells expressing wild-type FGFR3. U937 cells expressing mutated K650E FGFR3 showed more sensitivity to bortezomib than did the parental U937 cells. Furthermore, increased expression of Mcl-1 and decreased expression of NF-kappaB p65 suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through Bcl-2 and NF-kappaB signaling.
Conclusion:
Data from this study indicate that mutation status and the expression level of FGFR3 may be associated with bortezomib-related treatment resistance in lymphoma.
Insights
Fibroblast growth factor receptor 3 (FGFR3) expression impacts bortezomib effectiveness in lymphoma. FGFR3 mutations and expression levels may predict treatment resistance, influencing therapeutic outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Deregulated fibroblast growth factor receptor 3 (FGFR3) is implicated in various cancers, including lymphoma.
- Understanding FGFR3's role in lymphoma treatment response is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the association between fibroblast growth factor receptor 3 (FGFR3) expression and the therapeutic efficacy of bortezomib in lymphoma.
- To determine if FGFR3 mutation status influences bortezomib sensitivity or resistance.
Main Methods:
- Cell proliferation and apoptosis assays were conducted using U937 lymphoma cells.
- Comparisons were made between cells with minimal FGFR3 expression, wild-type FGFR3 overexpression, and Y373C or K650E mutant FGFR3 overexpression.
Main Results:
- Bortezomib-induced apoptosis in lymphoma cells correlated with FGFR3 expression levels.
- Overexpression of wild-type or Y373C mutant FGFR3 conferred resistance to bortezomib.
- K650E mutant FGFR3 expression increased sensitivity to bortezomib.
- Bortezomib resistance associated with wild-type and Y373C mutant FGFR3 may involve Bcl-2 and NF-kappaB signaling pathways.
Conclusions:
- FGFR3 expression levels and specific mutation statuses are potential biomarkers for bortezomib treatment resistance in lymphoma.
- These findings suggest that FGFR3 status could guide therapeutic decisions for lymphoma patients.
