دورية أكاديمية
Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma
| العنوان: | Maternal embryonic leucine zipper kinase is a novel target for diffuse large B cell lymphoma and mantle cell lymphoma |
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| المؤلفون: | Maes, Anke, Maes, Ken, Vlummens, Philip, De Raeve, Hendrik, Devin, Julie, Szablewski, Vanessa, De Veirman, Kim, Menu, Eline, Moreaux, Jerome, Vanderkerken, Karin, De Bruyne, Elke |
| المصدر: | BLOOD CANCER JOURNAL ; ISSN: 2044-5385 |
| سنة النشر: | 2019 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, PROMISING THERAPEUTIC TARGET, MELK, INHIBITOR, RITUXIMAB, GROWTH, PROLIFERATION, EXPRESSION, DISCOVERY, RADIATION, EFFICACY |
| الوصف: | Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are among the most aggressive B cell non-Hodgkin lymphomas. Maternal embryonic leucine zipper kinase (MELK) plays a role in cancer cell cycle progression and is associated with poor prognosis in several cancer cell types. In this study, the role of MELK in DLBCL and MCL and the therapeutic potential of MELK targeting is evaluated. MELK is highly expressed in DLBCL and MCL patient samples, correlating with a worse clinical outcome in DLBCL. Targeting MELK, using the small molecule OTSSP167, impaired cell growth and survival and induced caspase-mediated apoptosis in the lymphoma cells. Western blot analysis revealed that MELK targeting decreased the phosphorylation of FOXM1 and the protein levels of EZH2 and several mitotic regulators, such as Cdc25B, cyclin B1, Plk-1, and Aurora kinases. In addition, OTSSP167 also sensitized the lymphoma cells to the clinically relevant Bcl-2 inhibitor venetoclax by strongly reducing Mcl1 levels. Finally, OTSSP167 treatment of A20-inoculated mice resulted in a significant prolonged survival. In conclusion, targeting MELK with OTSSP167 induced strong anti-lymphoma activity both in vitro and in vivo. These findings suggest that MELK could be a potential new target in these aggressive B cell malignancies. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/8647024Test; http://hdl.handle.net/1854/LU-8647024Test; http://dx.doi.org/10.1038/s41408-019-0249-xTest; https://biblio.ugent.be/publication/8647024/file/8647025Test |
| DOI: | 10.1038/s41408-019-0249-x |
| الإتاحة: | https://doi.org/10.1038/s41408-019-0249-xTest https://biblio.ugent.be/publication/8647024Test http://hdl.handle.net/1854/LU-8647024Test https://biblio.ugent.be/publication/8647024/file/8647025Test |
| حقوق: | Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E8DCC5B8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41408-019-0249-x |
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