The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia
Open accessAbstract
N6-methyladenosine (m6A) is an abundant internal RNA modification1,2 that is catalysed predominantly by the METTL3–METTL14 methyltransferase complex3,4. The m6A methyltransferase METTL3 has been linked to the initiation and maintenance of acute myeloid leukaemia (AML), but the potential of therapeutic applications targeting this enzyme remains unknown5–7. Here we present the identification and characterization of STM2457, a highly potent and selective first-in-class catalytic inhibitor of METTL3, and a crystal structure of STM2457 in complex with METTL3–METTL14. Treatment of tumours with STM2457 leads to reduced AML growth and an increase in differentiation and apoptosis. These cellular effects are accompanied by selective reduction of m6A levels on known leukaemogenic mRNAs and a decrease in their expression consistent with a translational defect. We demonstrate that pharmacological inhibition of METTL3 in vivo leads to impaired engraftment and prolonged survival in various mouse models of AML, specifically targeting key stem cell subpopulations of AML. Collectively, these results reveal the inhibition of METTL3 as a potential therapeutic strategy against AML, and provide proof of concept that the targeting of RNA-modifying enzymes represents a promising avenue for anticancer therapy. Treatment with a specific inhibitor of the N6-methyladenosine methyltransferase METTL3 leads to reduced growth of cancer cells, indicating the potential of approaches targeting RNA-modifying enzymes for anticancer therapy.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters
Yu, G., Wang, L.-G., Han, Y., & He, Q.-Y. (2012) · OMICS: A Journal of Integrative Biology · doi:10.1089/omi.2011.0118 · Cited by 36,259
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype
Kim, D., Paggi, J. M., Park, C., Bennett, C., & Salzberg, S. L. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0201-4 · Cited by 15,022
Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
Meyer, K. D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C. E., & Jaffrey, S. R. (2012) · Cell · doi:10.1016/j.cell.2012.05.003 · Cited by 4,223
A METTL3–METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1432 · Cited by 3,433
Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9
Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W. C., Gilliland, D. G., et al. (2006) · Nature · doi:10.1038/nature04980 · Cited by 1,513
Cited by
Xiong, J., He, J., Zhu, J., Pan, J., Liao, W., Ye, H., Wang, H., Song, Y., Du, Y., Cui, B., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.02.033 · Cited by 804
Absolute quantification of single-base m6A methylation in the mammalian transcriptome using GLORI
Liu, C., Sun, H., Yi, Y., Shen, W., Li, K., Xiao, Y., Li, F., Li, Y., Hou, Y., Lu, B., et al. (2023) · Nature Biotechnology · doi:10.1038/s41587-022-01487-9 · Cited by 386
Epigenetics-targeted drugs: current paradigms and future challenges
Dai, W., Qiao, X., Fang, Y., Guo, R., Bai, P., Liu, S., Li, T., Jiang, Y., Wei, S., Na, Z., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02039-0 · Cited by 339
Wang, J.-N., Wang, F., Ke, J., Li, Z., Xu, C.-H., Yang, Q., Chen, X., He, X.-Y., He, Y., Suo, X.-G., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abk2709 · Cited by 298
Hidden codes in mRNA: Control of gene expression by m6A
Murakami, S., & Jaffrey, S. R. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.05.029 · Cited by 292
Metadata
- Authors
- Yankova, E., Blackaby, W., Albertella, M., Rak, J., De Braekeleer, E., Tsagkogeorga, G., Pilka, E. S., Aspris, D., Leggate, D., Hendrick, A. G., Webster, N. A., Andrews, B., Fosbeary, R., Guest, P., Irigoyen, N., Eleftheriou, M., Gozdecka, M., Dias, J. M. L., Bannister, A. J., Vick, B., Jeremias, I., Vassiliou, G. S., Rausch, O., Tzelepis, K., & Kouzarides, T.
- Venue
- Nature
- Published
- 2021-04-26
- Volume
- 593
- Issue
- 7860
- Pages
- 597-601
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3159494124
- Cited by
- 1,352
- References
- 10
- FWCI
- 55.35
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. https://app.cochat.ai/papers/10.1038/s41586-021-03536-w
- The paper
- Yankova, E., Blackaby, W., Albertella, M., Rak, J., De Braekeleer, E., Tsagkogeorga, G., Pilka, E. S., Aspris, D., Leggate, D., Hendrick, A. G., Webster, N. A., Andrews, B., Fosbeary, R., Guest, P., Irigoyen, N., Eleftheriou, M., Gozdecka, M., Dias, J. M. L., Bannister, A. J., . . . Kouzarides, T. (2021). Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. https://doi.org/10.1038/s41586-021-03536-w
Data sources
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.
