Academic Journal
Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses
| العنوان: | Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses |
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| المؤلفون: | Jana Trifinopoulos, Julia List, Thorsten Klampfl, Klara Klein, Michaela Prchal-Murphy, Agnieszka Witalisz-Siepracka, Florian Bellutti, Luca L. Fava, Gerwin Heller, Sarah Stummer, Patricia Testori, Monique L. den Boer, Judith M. Boer, Sonja Marinovic, Gregor Hoermann, Wencke Walter, Andreas Villunger, Piotr Sicinski, Veronika Sexl, Dagmar Gotthardt |
| المصدر: | Haematologica, Vol 999, Iss 1 (2024) |
| بيانات النشر: | Ferrata Storti Foundation, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs |
| مصطلحات موضوعية: | Diseases of the blood and blood-forming organs, RC633-647.5 |
| الوصف: | Despite major therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL), resistances and long-term toxicities still pose significant challenges. Cyclins and their associated cyclin-dependent kinases are one focus of cancer research when looking for targeted therapies. We discovered cyclin C as a key factor for B-ALL development and maintenance. While cyclin C is non-essential for normal hematopoiesis, CcncΔ/Δ BCR::ABL1+ B-ALL cells fail to elicit leukemia in mice. RNA sequencing experiments revealed a p53 pathway deregulation in CcncΔ/Δ BCR::ABL1+ cells resulting in the incapability of the leukemic cells to adequately respond to stress. A genome-wide CRISPR/Cas9 loss-of-function screen supplemented with additional knock-outs unveiled a dependency of human B-lymphoid cell lines on CCNC. High cyclin C levels in B-cell precursor (BCP) ALL patients were associated with poor event-free survival and increased risk of early disease recurrence after remission. Our findings highlight cyclin C as potential therapeutic target for B-ALL, particularly to enhance cancer cell sensitivity to stress and chemotherapy. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 0390-6078 1592-8721 |
| Relation: | https://haematologica.org/article/view/11781; https://doaj.org/toc/0390-6078; https://doaj.org/toc/1592-8721 |
| DOI: | 10.3324/haematol.2024.285701 |
| URL الوصول: | https://doaj.org/article/8800b97f24a34ac584683af5d6db62a8 |
| رقم الانضمام: | edsdoj.8800b97f24a34ac584683af5d6db62a8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 03906078 15928721 |
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| DOI: | 10.3324/haematol.2024.285701 |