دورية أكاديمية
Unveiling the signaling network of FLT3-ITD AML improves drug sensitivity prediction
| العنوان: | Unveiling the signaling network of FLT3-ITD AML improves drug sensitivity prediction |
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| المؤلفون: | Sara Latini, Veronica Venafra, Giorgia Massacci, Valeria Bica, Simone Graziosi, Giusj Monia Pugliese, Marta Iannuccelli, Filippo Frioni, Gessica Minnella, John Donald Marra, Patrizia Chiusolo, Gerardo Pepe, Manuela Helmer Citterich, Dimitros Mougiakakos, Martin Böttcher, Thomas Fischer, Livia Perfetto, Francesca Sacco |
| المصدر: | eLife, Vol 12 (2024) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | mouse, acute myeloid leukemia, tyrosine kinase, Boolean model, drug resistance, cancer therapy, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Currently, the identification of patient-specific therapies in cancer is mainly informed by personalized genomic analysis. In the setting of acute myeloid leukemia (AML), patient-drug treatment matching fails in a subset of patients harboring atypical internal tandem duplications (ITDs) in the tyrosine kinase domain of the FLT3 gene. To address this unmet medical need, here we develop a systems-based strategy that integrates multiparametric analysis of crucial signaling pathways, and patient-specific genomic and transcriptomic data with a prior knowledge signaling network using a Boolean-based formalism. By this approach, we derive personalized predictive models describing the signaling landscape of AML FLT3-ITD positive cell lines and patients. These models enable us to derive mechanistic insight into drug resistance mechanisms and suggest novel opportunities for combinatorial treatments. Interestingly, our analysis reveals that the JNK kinase pathway plays a crucial role in the tyrosine kinase inhibitor response of FLT3-ITD cells through cell cycle regulation. Finally, our work shows that patient-specific logic models have the potential to inform precision medicine approaches. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/90532Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.90532 |
| الوصول الحر: | https://doaj.org/article/046f6248d0ed4a4e8ed3337d150c805eTest |
| رقم الانضمام: | edsdoj.046f6248d0ed4a4e8ed3337d150c805e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.90532 |