Academic Journal
Biological significance of monoallelic and biallelic BIRC3 loss in del(11q) chronic lymphocytic leukemia progression
| العنوان: | Biological significance of monoallelic and biallelic BIRC3 loss in del(11q) chronic lymphocytic leukemia progression |
|---|---|
| المؤلفون: | Miguel Quijada-Álamo, María Hernández-Sánchez, Ana-Eugenia Rodríguez-Vicente, Claudia Pérez-Carretero, Alberto Rodríguez-Sánchez, Marta Martín-Izquierdo, Verónica Alonso-Pérez, Ignacio García-Tuñón, José María Bastida, María Jesús Vidal-Manceñido, Josefina Galende, Carlos Aguilar, José Antonio Queizán, Isabel González-Gascón y Marín, José-Ángel Hernández-Rivas, Rocío Benito, José Luis Ordóñez, Jesús-María Hernández-Rivas |
| المصدر: | Blood Cancer Journal, Vol 11, Iss 7, Pp 1-11 (2021) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | BIRC3 is monoallelically deleted in up to 80% of chronic lymphocytic leukemia (CLL) cases harboring del(11q). In addition, truncating mutations in the remaining allele of this gene can lead to BIRC3 biallelic inactivation, which has been shown to be a marker for reduced survival in CLL. Nevertheless, the biological mechanisms by which these lesions could contribute to del(11q) CLL pathogenesis and progression are partially unexplored. We implemented the CRISPR/Cas9-editing system to generate isogenic CLL cell lines harboring del(11q) and/or BIRC3 mutations, modeling monoallelic and biallelic BIRC3 loss. Our results reveal that monoallelic BIRC3 deletion in del(11q) cells promotes non-canonical NF-κB signaling activation via RelB-p52 nuclear translocation, being these effects allelic dose-dependent and therefore further enhanced in del(11q) cells with biallelic BIRC3 loss. Moreover, we demonstrate ex vivo in primary cells that del(11q) cases including BIRC3 within their deleted region show evidence of non-canonical NF-κB activation which correlates with high BCL2 levels and enhanced sensitivity to venetoclax. Furthermore, our results show that BIRC3 mutations in del(11q) cells promote clonal advantage in vitro and accelerate leukemic progression in an in vivo xenograft model. Altogether, this work highlights the biological bases underlying disease progression of del(11q) CLL patients harboring BIRC3 deletion and mutation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2044-5385 |
| Relation: | https://doi.org/10.1038/s41408-021-00520-5; https://doaj.org/toc/2044-5385; https://doaj.org/article/6298fa088832472aaa3af17d993dc8f6 |
| DOI: | 10.1038/s41408-021-00520-5 |
| الاتاحة: | https://doi.org/10.1038/s41408-021-00520-5 https://doaj.org/article/6298fa088832472aaa3af17d993dc8f6 |
| رقم الانضمام: | edsbas.E374DEBF |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20445385 |
|---|---|
| DOI: | 10.1038/s41408-021-00520-5 |