Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis
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 cel...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105820 https://orcid.org/0000-0002-6702-4192 |
| _version_ | 1826210393853263872 |
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| author | Wang, Ying-Hua Lee, Dongjun Yu, Vionnie W.C. Jeanson, Nathaniel T. Clish, Clary B. Cantley, Lewis C. Scadden, David T. Israelsen, William James Vander Heiden, Matthew G. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wang, Ying-Hua Lee, Dongjun Yu, Vionnie W.C. Jeanson, Nathaniel T. Clish, Clary B. Cantley, Lewis C. Scadden, David T. Israelsen, William James Vander Heiden, Matthew G. |
| author_sort | Wang, Ying-Hua |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:49:06Z |
| format | Article |
| id | mit-1721.1/105820 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:49:06Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1058202022-10-01T22:41:29Z Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis Wang, Ying-Hua Lee, Dongjun Yu, Vionnie W.C. Jeanson, Nathaniel T. Clish, Clary B. Cantley, Lewis C. Scadden, David T. Israelsen, William James Vander Heiden, Matthew G. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Israelsen, William James Vander Heiden, Matthew G. 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 2016-12-14T20:44:52Z 2016-12-14T20:44:52Z 2014-09 Article http://purl.org/eprint/type/JournalArticle 00928674 http://hdl.handle.net/1721.1/105820 Wang, Ying-Hua et al. “Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis.” Cell 158.6 (2014): 1309–1323. https://orcid.org/0000-0002-6702-4192 en_US http://dx.doi.org/10.1016/j.cell.2014.07.048 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Wang, Ying-Hua Lee, Dongjun Yu, Vionnie W.C. Jeanson, Nathaniel T. Clish, Clary B. Cantley, Lewis C. Scadden, David T. Israelsen, William James Vander Heiden, Matthew G. Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
| title | Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
| title_full | Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
| title_fullStr | Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
| title_full_unstemmed | Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
| title_short | Cell-State-Specific Metabolic Dependency in Hematopoiesis and Leukemogenesis |
| title_sort | cell state specific metabolic dependency in hematopoiesis and leukemogenesis |
| url | http://hdl.handle.net/1721.1/105820 https://orcid.org/0000-0002-6702-4192 |
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