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Updated: Sep 18, 2025
14:04
Neutrophil Isolation and Analysis to Determine their Role in Lymphoma Cell Sensitivity to Therapeutic Agents
Published on: March 25, 2016
15.5K
Resistance Mechanism for Zanubrutinib in Marginal Zone Lymphoma
John Sharp1, Arwa Y Shana'ah2, Timothy J Voorhees1
11Division of Hematology, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus, OH.
Summary
Brüton
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma often requiring multiple treatment lines.
- Brüton's tyrosine kinase inhibitors (BTKis) show promise for relapsed MZL, but resistance is a significant challenge.
Purpose of the Study:
- To report the first case of a patient with MZL developing co-mutations (BTK C481S and PLCG2 D334H) conferring BTKi resistance.
- To highlight disease progression and large cell transformation in a patient treated with zanubrutinib.
Main Methods:
- Case report of a patient with relapsed MZL treated with zanubrutinib.
- Genetic analysis to identify mutations associated with BTKi resistance.
Main Results:
- The patient developed large cell transformation of MZL.
- Acquisition of BTK C481S and PLCG2 D334H mutations was observed, predicting zanubrutinib resistance.
Conclusions:
- This case highlights the emergence of BTKi resistance mechanisms in MZL.
- Understanding these resistance pathways is crucial for developing new therapeutic strategies for MZL patients.
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