دورية أكاديمية
Biological Mechanisms And Clinical Implications Of Bcr-Abl-Induced Mitochondrial Oxidative Stress And Cell Survival In Chronic Myeloid Leukemia
| العنوان: | Biological Mechanisms And Clinical Implications Of Bcr-Abl-Induced Mitochondrial Oxidative Stress And Cell Survival In Chronic Myeloid Leukemia |
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| المؤلفون: | Zhang, Hui |
| المصدر: | Dissertations and Theses (Open Access) |
| بيانات النشر: | DigitalCommons@TMC |
| سنة النشر: | 2012 |
| المجموعة: | Houston Academy of Medicine-Texas Medical Center (HAM-TMC): DigitalCommons@The Texas Medical Center |
| مصطلحات موضوعية: | Chronic myeloid leukemia, CML, BCR-ABL, reactive oxygen species, ROS, GSH, BCL-XL, BCL-2, PEITC, Imatinib, ABT737, Hemic and Lymphatic Diseases, Medicine and Health Sciences |
| الوصف: | Chronic myeloid leukemia (CML), a myeloproliferative disorder, represents approximately 15-20% of all adult leukemia. The development of CML is clearly linked to the constitutively active protein-tyrosine kinase BCR-ABL, which is encoded by BCR-ABL fusion gene as the result of chromosome 9/22 translocation (Philadelphia chromosome). Previous studies have demonstrated that oxidative stress-associated genetic, metabolic and biological alterations contribute to CML cell survival and drug refractory. Mitochondria and NAD(P)H oxidase (NOX) are the major sources of BCR-ABL-induced cellular reactive oxygen species (ROS) production. However, it is still unknown how CML cells maintain the altered redox status, while escaping from the persistent oxidative stress-induced cell death. Therefore, elucidation of the mechanisms by which CML cells cope with oxidative stress will provide new insights into CML leukemogenesis. The major goal of this study is to identify the survival factors protecting CML cells against oxidative stress and develop novel therapeutic strategies to overcome drug resistance. Several experimental models were used to test CML cell redox status and cellular sensitivity to oxidative stress, including BCR-ABL inducible cell lines, BCR-ABL stably transformed cell lines and BCR-ABL-expressing CML blast crisis cells with differential BCL-XL/BCL-2 expressions. Additionally, an artificial CML cell model with heterogenic BCL-XL/BCL-2 expression was established to assess the correlation between differential survival factor expression patterns and cell sensitivity to Imatinib and oxidative stress. In this study, BCL-XL and GSH have been identified as the major survival factors responsive to BCR-ABL-promoted cellular oxidative stress and play a dominant role in regulating the threshold of oxidative stress-induced apoptosis. Cell survival factors BCL-XL and BCL-2 differentially protect mitochondria under oxidative stress. BCL-XL is an essential survival factor in preventing excessive ROS-induced cell death while ... |
| نوع الوثيقة: | text |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.library.tmc.edu/utgsbs_dissertations/224Test; https://digitalcommons.library.tmc.edu/context/utgsbs_dissertations/article/1254/viewcontent/auto_convert.pdfTest; https://digitalcommons.library.tmc.edu/context/utgsbs_dissertations/article/1254/filename/0/type/additional/viewcontent/Hui_Zhang_Thesis_front_pages.docTest |
| الإتاحة: | https://digitalcommons.library.tmc.edu/utgsbs_dissertations/224Test https://digitalcommons.library.tmc.edu/context/utgsbs_dissertations/article/1254/viewcontent/auto_convert.pdfTest https://digitalcommons.library.tmc.edu/context/utgsbs_dissertations/article/1254/filename/0/type/additional/viewcontent/Hui_Zhang_Thesis_front_pages.docTest |
| رقم الانضمام: | edsbas.6BAE40AB |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |