Academic Journal
Targeting the thioredoxin system as a novel strategy against B‐cell acute lymphoblastic leukemia
| العنوان: | Targeting the thioredoxin system as a novel strategy against B‐cell acute lymphoblastic leukemia |
|---|---|
| المؤلفون: | Klaudyna Fidyt, Agata Pastorczak, Agnieszka Goral, Kacper Szczygiel, Wojciech Fendler, Angelika Muchowicz, Marcin Adam Bartlomiejczyk, Joanna Madzio, Julia Cyran, Agnieszka Graczyk‐Jarzynka, Eugene Jansen, Elzbieta Patkowska, Ewa Lech‐Maranda, Deepali Pal, Helen Blair, Anna Burdzinska, Piotr Pedzisz, Eliza Glodkowska‐Mrowka, Urszula Demkow, Karolina Gawle‐Krawczyk, Michal Matysiak, Magdalena Winiarska, Przemyslaw Juszczynski, Wojciech Mlynarski, Olaf Heidenreich, Jakub Golab, Malgorzata Firczuk |
| المصدر: | Molecular Oncology, Vol 13, Iss 5, Pp 1180-1195 (2019) |
| بيانات النشر: | Wiley |
| سنة النشر: | 2019 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | ALL, antioxidant enzymes, leukemia, oxidative stress, peroxiredoxin, thioredoxin, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) is a genetically heterogeneous blood cancer characterized by abnormal expansion of immature B cells. Although intensive chemotherapy provides high cure rates in a majority of patients, subtypes harboring certain genetic lesions, such as MLL rearrangements or BCR‐ABL1 fusion, remain clinically challenging, necessitating a search for other therapeutic approaches. Herein, we aimed to validate antioxidant enzymes of the thioredoxin system as potential therapeutic targets in BCP‐ALL. We observed oxidative stress along with aberrant expression of the enzymes associated with the activity of thioredoxin antioxidant system in BCP‐ALL cells. Moreover, we found that auranofin and adenanthin, inhibitors of the thioredoxin system antioxidant enzymes, effectively kill BCP‐ALL cell lines and pediatric and adult BCP‐ALL primary cells, including primary cells cocultured with bone marrow‐derived stem cells. Furthermore, auranofin delayed the progression of leukemia in MLL‐rearranged patient‐derived xenograft model and prolonged the survival of leukemic NSG mice. Our results unveil the thioredoxin system as a novel target for BCP‐ALL therapy, and indicate that further studies assessing the anticancer efficacy of combinations of thioredoxin system inhibitors with conventional anti‐BCP‐ALL drugs should be continued. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| Relation: | https://doi.org/10.1002/1878-0261.12476; https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261; https://doaj.org/article/45a979d9ef364d65aa674b4bb09f8254 |
| DOI: | 10.1002/1878-0261.12476 |
| الاتاحة: | https://doi.org/10.1002/1878-0261.12476 https://doaj.org/article/45a979d9ef364d65aa674b4bb09f8254 |
| رقم الانضمام: | edsbas.937CF554 |
| قاعدة البيانات: | BASE |
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