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Published on: September 12, 2025
Establishment and characterization of therapy-resistant mantle cell lymphoma cell lines derived from different tissue
Adam K Ahrens1, Nagendra K Chaturvedi, Tara M Nordgren
1Department of Genetics, University of Nebraska Medical Center, Omaha, NE, USA.
Abstract:
Mantle cell lymphoma (MCL) is a rare but aggressive form of B cell non-Hodgkin lymphoma in which therapy resistance is common. New therapeutic options have extended survival in refractory MCL but have not provided durable remission. Tools are needed to assess the molecular and genetic changes associated with therapy resistance. Therefore, therapy-resistant MCL cell lines were established from the liver, kidney and lungs of human Granta 519-bearing NOD-SCID (non-obese diabetic-severe combined immunodeficiency) mice following treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy in combination with bortezomib. The cytomorphologies, immunophenotypes, growth patterns in semi-solid agar, cytogenetic profiles and gene expression differences between these cell lines were characterized to identify major changes associated with therapy resistance. Therapy-resistant cell lines exhibit more aggressive growth patterns and markedly different gene expression profiles compared to parental Granta 519 cells. Thus, these stable therapy-resistant cell lines are useful models to further study the molecular basis of drug resistance and to identify clinically relevant molecular targets in MCL.
Insights
Researchers developed new therapy-resistant mantle cell lymphoma (MCL) cell lines to study drug resistance. These models reveal significant genetic and growth pattern changes, aiding the search for new MCL treatment targets.
Area of Science:
- Oncology
- Hematology
- Cancer Biology
Background:
- Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma with frequent therapy resistance.
- Current treatments improve survival but rarely achieve durable remission in refractory MCL.
- Understanding the molecular basis of drug resistance is crucial for developing better therapies.
Purpose of the Study:
- To establish and characterize therapy-resistant mantle cell lymphoma cell lines.
- To identify molecular and genetic changes associated with drug resistance in MCL.
- To provide valuable models for studying MCL drug resistance and discovering new therapeutic targets.
Main Methods:
- Generation of therapy-resistant MCL cell lines from Granta 519 xenografts in NOD-SCID mice after CHOP chemotherapy and bortezomib treatment.
- Comprehensive characterization including cytomorphology, immunophenotyping, semi-solid agar growth, cytogenetics, and gene expression profiling.
- Comparison of resistant cell lines with parental Granta 519 cells to identify resistance-associated alterations.
Main Results:
- Established stable, therapy-resistant MCL cell lines from liver, kidney, and lung tissues.
- Resistant cell lines demonstrated more aggressive growth patterns compared to parental cells.
- Significant differences in gene expression profiles were observed between resistant and parental MCL cells.
Conclusions:
- The developed therapy-resistant MCL cell lines serve as robust models for investigating drug resistance mechanisms.
- These models facilitate the identification of key molecular changes driving resistance in MCL.
- The findings support the potential for discovering novel, clinically relevant molecular targets for MCL treatment.
