Pharmacologic inhibition of the ubiquitin-activating enzyme induces ER stress and apoptosis in chronic lymphocytic leukemia and ibrutinib-resistant mantle cell lymphoma cells
| Autor: | Scott R Best, Alexey V. Danilov, Nur Bruss, Tingting Liu, Allison Berger, Adam Kittai |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Chronic lymphocytic leukemia Apoptosis Lymphoma Mantle-Cell Ubiquitin-Activating Enzymes 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Piperidines immune system diseases hemic and lymphatic diseases Cell Line Tumor medicine Animals Humans Protein Kinase Inhibitors Multiple myeloma biology business.industry Bortezomib Cereblon Adenine Hematology medicine.disease Endoplasmic Reticulum Stress Leukemia Lymphocytic Chronic B-Cell Ubiquitin ligase Lymphoma Pyrimidines Oncology chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Ibrutinib biology.protein Cancer research Unfolded Protein Response Pyrazoles Mantle cell lymphoma business Proteasome Inhibitors Biomarkers 030215 immunology medicine.drug |
| Zdroj: | Leukemialymphoma. 60(12) |
| ISSN: | 1029-2403 |
| Popis: | With the advent of proteasome inhibitors (bortezomib) and pleiotropic pathway modulators which target cereblon E3 ligase (lenalidomide), the ubiquitin-proteasome system has emerged as a tractable target in non-Hodgkin lymphoma and multiple myeloma. Here we report that TAK-243, a small molecule inhibitor of the ubiquitin-activating enzyme (UAE), induced ER stress and the unfolded protein response in primary chronic lymphocytic leukemia cells, facilitating cell death. Moreover, targeting UAE was effective in ibrutinib-resistant mantle cell lymphoma cell lines and primary cells in vitro. Thus, UAE is a promising target in lymphoid malignancies, including ibrutinib-resistant lymphomas, an area of unmet medical need. |
| Databáze: | OpenAIRE |
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