The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification
Open accessAbstract
SUMMARY N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic messenger RNAs (mRNAs), plays critical roles in many bioprocesses. However, its functions in normal and malignant hematopoiesis remain elusive. Here we report METTL14, a key component of the m6A methyltransferase complex, is highly expressed in normal hematopoietic stem/progenitor cells (HSPCs) and acute myeloid leukemia (AML) cells carrying t(11q23), t(15;17), or t(8;21), and is down-regulated during myeloid differentiation. Silencing of METTL14 promotes terminal myeloid differentiation of normal HSPCs and AML cells, and inhibits AML cell survival/proliferation. METTL14 is required for development/maintenance of AML and self-renewal of leukemia stem/initiation cells (LSCs/LICs). Mechanistically, METTL14 exerts its oncogenic role by regulating its mRNA targets (e.g., MYB and MYC) through m6A modification, while itself is negatively regulated by SPI1. Collectively, our results reveal the SPI1⊣METTL14-MYB/MYC signaling axis in myelopoiesis and leukemogenesis, and highlight the critical roles of METTL14 and m6A modification in normal and malignant hematopoiesis.
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BackgroundSelf-citationComprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
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Self-citationDNMT3A Mutations in Acute Myeloid Leukemia
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Self-citationRole of RNA modifications in cancer
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Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally
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Metadata
- Authors
- Weng, H., Huang, H., Wu, H., Qin, X., Zhao, B. S., Dong, L., Shi, H., Skibbe, J., Shen, C., Hu, C., Sheng, Y., Wang, Y., Wunderlich, M., Zhang, B., Dore, L. C., Su, R., Deng, X., Ferchen, K., Li, C., Sun, M., Lu, Z., Jiang, X., Marcucci, G., Mulloy, J. C., Yang, J., Qian, Z., Wei, M., He, C., & Chen, J.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 22
- Issue
- 2
- Pages
- 191-205.e9
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2776540408
- Cited by
- 968
- References
- 16
- FWCI
- 25.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Weng, H., Huang, H., Wu, H., Qin, X., Zhao, B. S., Dong, L., Shi, H., Skibbe, J., Shen, C., Hu, C., Sheng, Y., Wang, Y., Wunderlich, M., Zhang, B., Dore, L. C., Su, R., Deng, X., Ferchen, K., Li, C., . . . Chen, J. (2018). METTL14 Inhibits Hematopoietic Stem/Progenitor Differentiation and Promotes Leukemogenesis via mRNA m6A Modification. Cell Stem Cell. https://doi.org/10.1016/j.stem.2017.11.016
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