Academic Journal
Response to Bruton's tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy.
| العنوان: | Response to Bruton's tyrosine kinase inhibitors in aggressive lymphomas linked to chronic selective autophagy. |
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| المؤلفون: | Phelan, James D, Scheich, Sebastian, Choi, Jaewoo, Wright, George W, Häupl, Björn, Young, Ryan M, Rieke, Sara A, Pape, Martine, Ji, Yanlong, Urlaub, Henning, Bolomsky, Arnold, Doebele, Carmen, Zindel, Alena, Wotapek, Tanja, Kasbekar, Monica, Collinge, Brett, Huang, Da Wei, Coulibaly, Zana A, Morris, Vivian M, Zhuang, Xiaoxuan, Enssle, Julius C, Yu, Xin, Xu, Weihong, Yang, Yandan, Zhao, Hong, Wang, Zhuo, Tran, Andy D, Shoemaker, Christopher J, Shevchenko, Galina, Hodson, Daniel J, Shaffer, Arthur L, Staudt, Louis M, Oellerich, Thomas |
| بيانات النشر: | Elsevier BV //dx.doi.org/10.1016/j.ccell.2023.12.019 Cancer Cell |
| سنة النشر: | 2024 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Bruton’s tyrosine kinase, DLBCL, autophagy, functional genomics, proteomics, targeted therapy, Humans, Tyrosine Kinase Inhibitors, Myeloid Differentiation Factor 88, Signal Transduction, Lymphoma, Large B-Cell, Diffuse |
| الوصف: | Diffuse large B cell lymphoma (DLBCL) is an aggressive, profoundly heterogeneous cancer, presenting a challenge for precision medicine. Bruton's tyrosine kinase (BTK) inhibitors block B cell receptor (BCR) signaling and are particularly effective in certain molecular subtypes of DLBCL that rely on chronic active BCR signaling to promote oncogenic NF-κB. The MCD genetic subtype, which often acquires mutations in the BCR subunit, CD79B, and in the innate immune adapter, MYD88L265P, typically resists chemotherapy but responds exceptionally to BTK inhibitors. However, the underlying mechanisms of response to BTK inhibitors are poorly understood. Herein, we find a non-canonical form of chronic selective autophagy in MCD DLBCL that targets ubiquitinated MYD88L265P for degradation in a TBK1-dependent manner. MCD tumors acquire genetic and epigenetic alterations that attenuate this autophagic tumor suppressive pathway. In contrast, BTK inhibitors promote autophagic degradation of MYD88L265P, thus explaining their exceptional clinical benefit in MCD DLBCL. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://www.repository.cam.ac.uk/handle/1810/363676; https://doi.org/10.17863/CAM.105642 |
| DOI: | 10.17863/CAM.105642 |
| الاتاحة: | https://www.repository.cam.ac.uk/handle/1810/363676 https://doi.org/10.17863/CAM.105642 |
| Rights: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.E463AC67 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.105642 |
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