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HomeNatureMetformin reduces the competitive advantage of Dnmt3aR878H HSPCs

Metformin reduces the competitive advantage of Dnmt3aR878H HSPCs

  • Jaiswal, S. et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N. Engl. J. Med. 377, 111–121 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jaiswal, S. et al. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371, 2488–2498 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Genovese, G. et al. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med. 371, 2477–2487 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weeks, L. D. & Ebert, B. L. Causes and consequences of clonal hematopoiesis. Blood 142, 2235–2246 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bick, A. G. et al. Inherited causes of clonal haematopoiesis in 97,691 whole genomes. Nature 586, 763–768 (2020).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buscarlet, M. et al. DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions. Blood 130, 753–762 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ley, T. J. et al. DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 363, 2424–2433 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bridges, H. R. et al. Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides. Science 379, 351–357 (2023).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Venugopal, K., Feng, Y., Shabashvili, D. & Guryanova, O. A. Alterations to DNMT3A in hematologic malignancies. Cancer Res. 81, 254–263 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Young, A. L., Tong, R. S., Birmann, B. M. & Druley, T. E. Clonal hematopoiesis and risk of acute myeloid leukemia. Haematologica 104, 2410–2417 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jawad, M. et al. DNMT3A R882 mutations confer unique clinicopathologic features in MDS including a high risk of AML transformation. Front. Oncol. 12, 849376 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Larsson, C. A., Cote, G. & Quintas-Cardama, A. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol. Cancer Res. 11, 815–827 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Russler-Germain, D. A. et al. The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers. Cancer Cell 25, 442–454 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, S. J. et al. A DNMT3A mutation common in AML exhibits dominant-negative effects in murine ES cells. Blood 122, 4086–4089 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smith, A. M. et al. Functional and epigenetic phenotypes of humans and mice with DNMT3A overgrowth syndrome. Nat. Commun. 12, 4549 (2021).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Loberg, M. A. et al. Sequentially inducible mouse models reveal that Npm1 mutation causes malignant transformation of Dnmt3a-mutant clonal hematopoiesis. Leukemia 33, 1635–1649 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nam, A. S. et al. Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation. Nat. Genet. 54, 1514–1526 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • LaMoia, T. E. & Shulman, G. I. Cellular and molecular mechanisms of metformin action. Endocr. Rev. 42, 77–96 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Seo, B. B. et al. Molecular remedy of complex I defects: rotenone-insensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae mitochondria restores the NADH oxidase activity of complex I-deficient mammalian cells. Proc. Natl Acad. Sci. USA 95, 9167–9171 (1998).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wheaton, W. W. et al. Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. eLife 3, e02242 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dowling, R. J. et al. Metformin pharmacokinetics in mouse tumors: implications for human therapy. Cell Metab. 23, 567–568 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Izzo, F. et al. DNA methylation disruption reshapes the hematopoietic differentiation landscape. Nat. Genet. 52, 378–387 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ducker, G. S. et al. Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma. Proc. Natl Acad. Sci. USA 114, 11404–11409 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Konteatis, Z. et al. Discovery of AG-270, a first-in-class oral MAT2A inhibitor for the treatment of tumors with homozygous MTAP deletion. J. Med. Chem. 64, 4430–4449 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dai, Y. J. et al. Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement. Proc. Natl Acad. Sci. USA 114, 5237–5242 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fiumara, M. et al. Genotoxic effects of base and prime editing in human hematopoietic stem cells. Nat. Biotechnol. 42, 877–891 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cuyas, E. et al. Metformin regulates global DNA methylation via mitochondrial one-carbon metabolism. Oncogene 37, 963–970 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cuyas, E. et al. Metformin directly targets the H3K27me3 demethylase KDM6A/UTX. Aging Cell 17, e12772 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Garcia-Calzon, S. et al. DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes. Diabetes Res. Clin. Pract. 202, 110807 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kristensen, D. T. et al. Metformin use and risk of myeloproliferative neoplasms: a Danish population-based case–control study. Blood Adv. 8, 4478–4485 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nelson, J. W. et al. Engineered pegRNAs improve prime editing efficiency. Nat. Biotechnol. 40, 402–410 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Akalin, A. et al. methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 13, R87 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Akalin, A. et al. Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia. PLoS Genet. 8, e1002781 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, H. Q., Tuominen, L. K. & Tsai, C. J. SLIM: a sliding linear model for estimating the proportion of true null hypotheses in datasets with dependence structures. Bioinformatics 27, 225–231 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • Lee, S., Cook, D. & Lawrence, M. plyranges: a grammar of genomic data transformation. Genome Biol. 20, 4 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, Q. et al. Exploring epigenomic datasets by ChIPseeker. Curr. Protoc. 2, e585 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yu, G., Wang, L. G. & He, Q. Y. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382–2383 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gehrke, S. et al. Red blood cell metabolic responses to torpor and arousal in the hibernator Arctic ground squirrel. J. Proteome Res. 18, 1827–1841 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nemkov, T., Reisz, J. A., Gehrke, S., Hansen, K. C. & D’Alessandro, A. High-throughput metabolomics: isocratic and gradient mass spectrometry-based methods. Methods Mol. Biol. 1978, 13–26 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nemkov, T., Hansen, K. C. & D’Alessandro, A. A three-minute method for high-throughput quantitative metabolomics and quantitative tracing experiments of central carbon and nitrogen pathways. Rapid Commun. Mass Spectrom. 31, 663–673 (2017).

    Article 
    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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