Dissertation/ Thesis
Metabolic reprogramming in chronic lymphocytic leukemia : role of peroxisomal fatty acid β-oxidation as an energy supplier ; La reprogrammation métabolique dans la leucémie lymphoïde chronique : rôle de la β-oxydation peroxysomale des acides gras comme source d'énergie
| العنوان: | Metabolic reprogramming in chronic lymphocytic leukemia : role of peroxisomal fatty acid β-oxidation as an energy supplier ; La reprogrammation métabolique dans la leucémie lymphoïde chronique : rôle de la β-oxydation peroxysomale des acides gras comme source d'énergie |
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| المؤلفون: | Tannoury, Mariana |
| المساهمون: | Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris-Saclay, Santos Susin, Delphine Garnier |
| المصدر: | https://theses.hal.science/tel-04433508 ; Cancer. Université Paris-Saclay, 2023. English. ⟨NNT : 2023UPASL089⟩. |
| بيانات النشر: | CCSD |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Fatty acid metabolism, Peroxisomes, Chronic lymphocytic leukemia, ACOX1, Mitochondria, Anti-Tumor therapy, Métabolisme des acides gras, Peroxysomes, Leucémie lymphoide chronique, Mitochondries, Thérapie anti-Tumorale, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology |
| الوصف: | Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in Western countries. It is characterized by the accumulation of CD5+ monoclonal B lymphocytes in peripheral blood, bone marrow, and secondary lymphoid organs. CLL prognosis depends on the clinical stage and biological markers, including IGHV mutational status, cytogenetic abnormalities such as del11q and del17p, or karyotype complexity. Despite excellent clinical results obtained with Bruton tyrosine kinase (BTK) or BCL-2 inhibitors, drug resistance due to the emergence of genetic mutations (e.g. mutations in BTK, BCL-2, del8p, etc.) remains a major cause of treatment failure. Indeed, no complete remission is guaranteed, so ongoing scientific exploration is necessary to develop innovative therapeutic strategies.Studies of cancer cell metabolism have recently gained significant relevance with the recognition of “metabolic reprogramming” as an essential hallmark of the tumor phenotype. A major part of research is focused on ATP, the cell's energy currency, which orchestrates essential cellular functions (e.g. proliferation, macromolecules biosynthesis, etc.). Deciphering metabolic adaptations can then reveal potential vulnerabilities specific to tumor cells. Selectively disrupting this tumor reprogramming opens up promising avenues for cancer treatment. Furthermore, targeting metabolic vulnerabilities in combination with existing therapeutic drugs appears to be a compelling strategy for improving treatment efficacy. Hence, my thesis project aims to identify a metabolic specificity characterizing malignant CLL B-lymphocytes, focusing on a potential metabolic pathway that could be key to ATP generation in these tumor cells.I thus demonstrated an increase in mitochondrial oxidative phosphorylation (OXPHOS) in CLL CD5+ B-cells compared to healthy CD5- B-cells suggesting a predominance of mitochondrial ATP generation. The use of glucose as a metabolic intermediate for OXPHOS was excluded and an initial mRNAseq approach revealed overexpression ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | English |
| Relation: | NNT: 2023UPASL089 |
| الاتاحة: | https://theses.hal.science/tel-04433508 https://theses.hal.science/tel-04433508v1/document https://theses.hal.science/tel-04433508v1/file/120660_TANNOURY_2023_archivage.pdf |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.D8898A49 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |