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Updated: Jun 24, 2026

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
Published on: May 1, 2015
Bortezomib therapeutic effect is associated with expression of FGFR3 in multiple myeloma cells
Min Guan1, Lijun Zhu, George Somlo
1Department of Clinical Molecular Pharmacology, Division of Medical Oncology and Therapeutic Research, City of Hope National Medical Center, Duarte, CA, 91010, USA.
Unlabelled:
The ectopically expressed and deregulated fibroblast growth factor receptor 3 (FGFR3) has been observed in approximately 20% of multiple myeloma (MM) patients. In this study, we investigated whether the therapeutic effect of bortezomib is associated with FGFR3 expression.
Materials And Methods:
Cell proliferation and apoptosis assays were performed in minimal FGFR3 expressing U266 cells and compared to U266 cells overexpressing FGFR3 wild-type (T-U266), or Y373C (Y-U266) or K650E (K-U266) mutant FGFR3.
Results:
Our results suggested cell survival decreases in a dose-dependent manner. Interestingly, expression of FGFR3 protein was similarly dose dependent on bortezomib. It is confirmed the bortezomib-induced apoptotic death is correlated with FGFR3 expression. Furthermore, increased expression of p-STAT3, Mcl-1 and VEGF suggested that bortezomib resistance associated with Y373C mutation and wild-type FGFR3 may be partly mediated through p-STAT3 signaling.
Conclusion:
Our data indicates that Y373C mutation and wild-type FGFR3 may be associated with bortezomib-related treatment resistance in multiple myeloma.
Insights
Fibroblast growth factor receptor 3 (FGFR3) expression correlates with bortezomib efficacy in multiple myeloma. Elevated FGFR3, particularly Y373C mutations, may indicate resistance to bortezomib treatment.
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Fibroblast growth factor receptor 3 (FGFR3) is deregulated in about 20% of multiple myeloma (MM) cases.
- The role of FGFR3 expression in MM treatment response remains unclear.
Purpose of the Study:
- To investigate the association between FGFR3 expression and the therapeutic efficacy of bortezomib in multiple myeloma.
- To determine if specific FGFR3 mutations influence bortezomib response.
Main Methods:
- Cell proliferation and apoptosis assays were conducted.
- U266 cells with varying levels of FGFR3 expression (wild-type, Y373C mutant, K650E mutant) were utilized.
- Western blotting was used to assess protein expression levels.
Main Results:
- Bortezomib treatment reduced cell survival in a dose-dependent manner.
- FGFR3 protein expression levels were also dose-dependent on bortezomib.
- Bortezomib-induced apoptosis was correlated with FGFR3 expression.
- Increased p-STAT3, Mcl-1, and VEGF expression suggested bortezomib resistance associated with Y373C mutation and wild-type FGFR3, potentially mediated by p-STAT3 signaling.
Conclusions:
- FGFR3 expression, including wild-type and Y373C mutations, is linked to bortezomib resistance in multiple myeloma.
- The p-STAT3 signaling pathway may play a role in mediating this resistance.
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