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Cited by 502

The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.

Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia

Open access
Paris, Jasmin, Morgan, Marcos, Campos, Joana, Spencer, Gary J., Shmakova, Alena, Ivanova, Ivayla, Mapperley, Christopher, Lawson, Hannah, Wotherspoon, David A., Sepulveda, Catarina, Vukovic, Milica, Allen, Lewis, Sarapuu, Annika, Tavosanis, Andrea, Guitart, Amelie V., Villacreces, Arnaud, Much, Christian, Choe, Junho, Azar, Ali, van de Lagemaat, Louie N., Vernimmen, Douglas, Nehme, Ali, Mazurier, Frederic, Somervaille, Tim C.P., Gregory, Richard I., O’Carroll, Dónal, Kranc, Kamil R.·2019·Cell Stem Cell

Abstract

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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Crossref · 10.1016/j.stem.2019.03.021

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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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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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