کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10907248 | 1087398 | 2016 | 21 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Oxidative stress and hypoxia in normal and leukemic stem cells
ترجمه فارسی عنوان
استرس اکسیداتیو و هیپوکسیا در سلول های بنیادی طبیعی و لوسمی
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
چکیده انگلیسی
The main hematopoietic stem cell (HSC) functions, self-renewal and differentiation, are finely regulated by both intrinsic mechanisms such as transcriptional and epigenetic regulators and extrinsic signals originating in the bone marrow microenvironment (HSC niche) or in the body (humoral mediators). The interaction between regulatory signals and cellular metabolism is an emerging area. Several metabolic pathways function differently in HSCs compared with progenitors and differentiated cells. Hypoxia, acting through hypoxia-inducing factors, has emerged as a key regulator of stem cell biology and acts by maintaining HSC quiescence and a condition of metabolic dormancy based on anaerobic glycolytic energetic metabolism, with consequent low production reactive oxygen species (ROS) and high antioxidant defense. Hematopoietic cell differentiation is accompanied by changes in oxidative metabolism (decrease of anaerobic glycolysis and increase of oxidative phosphorylation) and increased levels of ROS. Leukemic stem cells, defined as the cells that initiate and maintain the leukemic process, show peculiar metabolic properties in that they are more dependent on oxidative respiration than on glycolysis and are more sensitive to oxidative stress than normal HSCs. Several mitochondrial abnormalities have been described in acute myeloid leukemia (AML) cells, explaining the shift to aerobic glycolysis observed in these cells and offering the unique opportunity for therapeutic metabolic targeting. Finally, frequent mutations of the mitochondrial isocitrate dehydrogenase-2 (IDH2) enzyme are observed in AML cells, in which the mutated enzyme acts as an oncogenic driver and can be targeted using specific inhibitors under clinical evaluation with promising results.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Hematology - Volume 44, Issue 7, July 2016, Pages 540-560
Journal: Experimental Hematology - Volume 44, Issue 7, July 2016, Pages 540-560
نویسندگان
Ugo Testa, Catherine Labbaye, Germana Castelli, Elvira Pelosi,