The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition
Open accessAbstract
Somatic mutations in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 occur frequently in acute myeloid leukemia (AML) and other cancers. These genes encode neomorphic proteins that produce the presumed oncometabolite 2-hydroxyglutarate (2-HG). Despite the prospect of treating AML and other cancers by targeting IDH mutant proteins, it remains unclear how these mutants affect tumor development and maintenance in vivo, and no cancer models exist to study the action of IDH2 mutants in vivo. We show that IDH2 mutants can cooperate with oncogenic Flt3 or Nras alleles to drive leukemia in mice by impairing the differentiation of cells of the myeloid lineage. Pharmacologic or genetic inhibition of IDH2 triggers the differentiation and death of AML cells, albeit only with prolonged IDH2 inhibition. In contrast, inhibition of the bromodomain-containing protein Brd4 triggers rapid differentiation and death of IDH2 mutant AML. Our results establish a critical role for mutant IDH2 in leukemogenesis and tumor maintenance and identify an IDH-independent strategy to target these cancers therapeutically.
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Cites
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
IDH1 and IDH2 Mutations in Gliomas
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Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Self-citationCancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citationXu, W., Yang, H., Liu, Y., Yang, Y., Wang, P., Kim, S.-H., Ito, S., Yang, C., Wang, P., Xiao, M.-T., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.12.014 · Cited by 2,875
Self-citationFigueroa, M. E., Abdel-Wahab, O., Lu, C., Ward, P. S., Patel, J., Shih, A., Li, Y., Bhagwat, N., Vasanthakumar, A., Fernandez, H. F., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.015 · Cited by 2,766
Self-citationRecurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219
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Self-citationIDH mutation impairs histone demethylation and results in a block to cell differentiation
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Understanding the Intersections between Metabolism and Cancer Biology
Vander Heiden, M. G., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,293
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Dang, L., Yen, K., & Attar, E. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw013 · Cited by 509
AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations
Yen, K., Travins, J., Wang, F., David, M. D., Artin, E., Straley, K., Padyana, A., Gross, S., DeLaBarre, B., Tobin, E., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1034 · Cited by 471
Extreme vulnerability of IDH1 mutant cancers to NAD+ depletion
Tateishi, K., Wakimoto, H., Iafrate, A. J., Tanaka, S., Loebel, F., Lelic, N., Wiederschain, D., Bedel, O., Deng, G., Zhang, B., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.11.006 · Cited by 433
Metadata
- Authors
- Chen, C., Liu, Y., Lu, C., Cross, J. R., Morris, J. P., Shroff, A. S., Ward, P. S., Bradner, J. E., Thompson, C., & Lowe, S. W.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-09-15
- Volume
- 27
- Issue
- 18
- Pages
- 1974-1985
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2155106329
- Cited by
- 182
- References
- 19
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition. https://app.cochat.ai/papers/10.1101/gad.226613.113
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- Chen, C., Liu, Y., Lu, C., Cross, J. R., Morris, J. P., Shroff, A. S., Ward, P. S., Bradner, J. E., Thompson, C., & Lowe, S. W. (2013). Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition. Genes & Development. https://doi.org/10.1101/gad.226613.113
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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