The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia
Open accessAbstract
SUMMARY Inhibition of the Menin (MEN1) and MLL (MLL1, KMT2A) interaction is a potential therapeutic strategy for MLL-rearranged (MLL-r) leukemia. Structure-based design yielded the potent, highly selective and orally-bioavailable small molecule inhibitor VTP50469. Cell lines carrying MLL-rearrangements were selectively responsive to VTP50469. VTP50469 displaced Menin from protein complexes and inhibited chromatin occupancy of MLL at select genes. Loss of MLL binding led to changes in gene expression, differentiation, and apoptosis. Patient-derived xenograft (PDX) models derived from patients with either MLL-r AML or MLL-r ALL showed dramatic reductions of leukemia burden when treated with VTP50469. Multiple mice engrafted with MLL-r ALL remained disease free greater than one year after treatment. These data support rapid translation of this approach to clinical trials.
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Cites
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Cited by
The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia
Issa, G. C., Aldoss, I., DiPersio, J., Cuglievan, B., Stone, R., Arellano, M., Thirman, M. J., Patel, M. R., Dickens, D. S., Shenoy, S., et al. (2023) · Nature · doi:10.1038/s41586-023-05812-3 · Cited by 507
Self-citationTherapeutic targeting of preleukemia cells in a mouse model of NPM1 mutant acute myeloid leukemia
Uckelmann, H. J., Kim, S. M., Wong, E. M., Hatton, C., Giovinazzo, H., Gadrey, J. Y., Krivtsov, A. V., Rücker, F. G., Döhner, K., McGeehan, G. M., et al. (2020) · Science · doi:10.1126/science.aax5863 · Cited by 257
Self-citationChen, J., Zhao, L., Peng, H., Dai, S., Quan, Y., Wang, M., Wang, J., Bi, Z., Zheng, Y., Zhou, S., et al. (2021) · Cancer Gene Therapy · doi:10.1038/s41417-020-0190-y · Cited by 46
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Self-citationA distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia
(2022) · doi:10.1101/gad.349284.121 · Cited by 31
Metadata
- Authors
- Krivtsov, A. V., Evans, K., Gadrey, J. Y., Eschle, B. K., Hatton, C., Uckelmann, H. J., Ross, K. N., Perner, F., Olsen, S. N., Pritchard, T., McDermott, L., Jones, C. D., Jing, D., Braytee, A., Chacon, D., Earley, E., McKeever, B. M., Claremon, D., Gifford, A. J., Lee, H. J., Teicher, B. A., Pimanda, J. E., Beck, D., Perry, J. A., Smith, M. A., McGeehan, G. M., Lock, R. B., & Armstrong, S. A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 36
- Issue
- 6
- Pages
- 660-673.e11
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2993435749
- Cited by
- 447
- References
- 66
- FWCI
- 25.53
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. https://app.cochat.ai/papers/10.1016/j.ccell.2019.11.001
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- Krivtsov, A. V., Evans, K., Gadrey, J. Y., Eschle, B. K., Hatton, C., Uckelmann, H. J., Ross, K. N., Perner, F., Olsen, S. N., Pritchard, T., McDermott, L., Jones, C. D., Jing, D., Braytee, A., Chacon, D., Earley, E., McKeever, B. M., Claremon, D., Gifford, A. J., . . . Armstrong, S. A. (2019). A Menin-MLL Inhibitor Induces Specific Chromatin Changes and Eradicates Disease in Models of MLL-Rearranged Leukemia. Cancer Cell. https://doi.org/10.1016/j.ccell.2019.11.001
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
