ArticleInternational journal of clinical oncology2019
Cell-type-specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells.
Article in International journal of clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Single-cell RNA-seq reveals diverse molecular signatures associated with Methotrexate resistance in primary central nervous system lymphoma cells.Journal of neuro-oncology · 2025Article
- Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.Scientifica · 2025Review
- Extranodal lymphoma: pathogenesis, diagnosis and treatment.Molecular biomedicine · 2023Review
- Article
- Relapsed Primary Central Nervous System Lymphoma: Current Advances.Frontiers in oncology · 2021Review
- GSEA-assisted gene signatures valid for combinations of prognostic markers in PCNSL.Scientific reports · 2020Article
- Review
- Molecular Mechanisms and Therapeutic Prospects of Immunotherapy and Targeted Therapy in Primary Central Nervous System Lymphoma.Technology in cancer research & treatmentReview
- Proteomic Profiling Reveals HECTD4-dependent Regulation of Protein Ubiquitination and Signaling Pathways in Prostate Cancer.Cancer genomics & proteomicsArticle
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMethotrexate (MTX) is used in first-line treatment of primary central nervous system lymphoma (PCNSL), but most cases result in relapse-acquired resistance to MTX. However, only few studies have reported on internal changes and chemotherapies in PCNSL.
methodsIn this study, we generated two MTX-resistant PCNSL cell lines, designated MTX-HKBML and MTX-TK, in addition to a MTX-resistant Burkitt lymphoma cell line, designated MTX-RAJI. We examined gene expression changes and drug sensitivity to a proteasome inhibitor, bortezomib, in these cells.
resultsCytotoxic tests revealed that the 50% inhibitory concentration for MTX in MTX-HKBML is markedly higher than that in the other two cell lines. Expression of the genes in MTX and folate metabolisms, including gamma-glutamyl hydrolase and dihydrofolate reductase, are upregulated in both MTX-HKBML and MTX-TK, whereas the gene expression of folylpolyglutamate synthetase, thymidylate synthase, and methylenetetrahydrofolate dehydrogenase 1 were upregulated and downregulated in MTX-HKBML and MTX-TK, respectively, on the other hand, bortezomib sensitivity was observed in MTX-TK, as compared with control TK, but not in MTX-HKBML.
conclusionThese results indicate the cell-type-specific changes downstream of metabolic pathways for MTX and folate, bortezomib sensitivity, and purine and pyrimidine syntheses, in each PCNSL cell line. The MTX-resistant lymphoma cell lines established may be useful for in vitro relapse models for MTX and development of salvage chemotherapy and drug discovery.
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