Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis
| العنوان: | Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
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| المؤلفون: | David T. Scadden, Clary B. Clish, Dongjun Lee, Lewis C. Cantley, Ying-Hua Wang, Matthew G. Vander Heiden, William J. Israelsen, Vionnie W.C. Yu, Nathaniel T. Jeanson |
| المساهمون: | Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Israelsen, William James, Vander Heiden, Matthew G. |
| المصدر: | PMC |
| بيانات النشر: | Elsevier BV, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Lactate dehydrogenase A, Pyruvate Kinase, Biology, PKM2, General Biochemistry, Genetics and Molecular Biology, Mice, Mice, Congenic, medicine, Animals, Humans, Glycolysis, Progenitor cell, education, education.field_of_study, Leukemia, L-Lactate Dehydrogenase, Biochemistry, Genetics and Molecular Biology(all), Hematopoietic Stem Cells, medicine.disease, Hematopoiesis, 3. Good health, Isoenzymes, Mice, Inbred C57BL, Anaerobic glycolysis, Cancer research, Lactate Dehydrogenase 5, Stem cell, Gene Deletion, Pyruvate kinase |
| الوصف: | The balance between oxidative and non-oxidative glucose metabolism is essential for a number of pathophysiological processes. By deleting enzymes that affect aerobic glycolysis with different potencies, we examine how modulating glucose metabolism specifically affects hematopoietic and leukemic cell populations. We find that deficiency in the M2 pyruvate kinase isoform (PKM2) reduces levels of metabolic intermediates important for biosynthesis and impairs progenitor function without perturbing hematopoietic stem cells (HSC), whereas lactate dehydrogenase-A (LDHA) deletion significantly inhibits the function of both HSC and progenitors during hematopoiesis. In contrast, leukemia initiation by transforming alleles putatively affecting either HSC or progenitors is inhibited in the absence of either PKM2 or LDHA, indicating that the cell state-specific responses to metabolic manipulation in hematopoiesis do not apply to the setting of leukemia. This finding suggests that fine-tuning the level of glycolysis may be therapeutically explored for treating leukemia while preserving HSC function. National Institutes of Health (U.S.) (Grants P30CA147882 and R01CA168653) Smith Family Foundation Burroughs Wellcome Fund Virginia and D.K. Ludwig Fund for Cancer Research Damon Runyon Cancer Research Foundation |
| وصف الملف: | application/pdf |
| تدمد: | 0092-8674 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1cd965a6182d6824416ce2f0b521aa1 https://doi.org/10.1016/j.cell.2014.07.048 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a1cd965a6182d6824416ce2f0b521aa1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00928674 |
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