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Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia
Open accessAbstract
Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). Here, we show that the mRNA m 6 A reader YTHDF2 is overexpressed in a broad spectrum of human AML and is required for disease initiation as well as propagation in mouse and human AML. YTHDF2 decreases the half-life of diverse m 6 A transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2 , whose upregulation in Ythdf2 -deficient LSCs primes cells for apoptosis. Intriguingly, YTHDF2 is not essential for normal HSC function, with YTHDF2 deficiency actually enhancing HSC activity. Thus, we identify YTHDF2 as a unique therapeutic target whose inhibition selectively targets LSCs while promoting HSC expansion.
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Metadata
- Authors
- Paris, J., Morgan, M., Campos, J., Spencer, G. J., Shmakova, A., Ivanova, I., Mapperley, C., Lawson, H., Wotherspoon, D. A., Sepulveda, C., Vukovic, M., Allen, L., Sarapuu, A., Tavosanis, A., Guitart, A. V., Villacreces, A., Much, C., Choe, J., Azar, A., van de Lagemaat, L. N., Vernimmen, D., Nehme, A., Mazurier, F., Somervaille, T. C. P., Gregory, R. I., O’Carroll, D., & Kranc, K. R.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 25
- Issue
- 1
- Pages
- 137-148.e6
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2941333182
- Cited by
- 502
- References
- 78
- FWCI
- 20.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. https://app.cochat.ai/papers/10.1016/j.stem.2019.03.021
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- Paris, J., Morgan, M., Campos, J., Spencer, G. J., Shmakova, A., Ivanova, I., Mapperley, C., Lawson, H., Wotherspoon, D. A., Sepulveda, C., Vukovic, M., Allen, L., Sarapuu, A., Tavosanis, A., Guitart, A. V., Villacreces, A., Much, C., Choe, J., Azar, A., . . . Kranc, K. R. (2019). Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. Cell Stem Cell. https://doi.org/10.1016/j.stem.2019.03.021
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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.
