ArticleGenes & development2015
Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03217903 (High Risk Myelodysplasia Treated by Azacytidine), which is not on this map. Cited by 182 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
High Risk Myelodysplasia Treated by Azacytidine : Genetic and Epigenetic (MYRAGE)
Who cites it
182 citing papers in PubMed, 260 citations in OpenAlex.
- Vitamin C boosts DNA demethylation in TET2 germline mutation carriers.Clinical epigenetics · 2023Trial
- Trial
- Developmental timing distinguishes pediatric and adult cancers through retention and rewiring mechanisms.Nature communications · 2026Review
- Pre-diagnostic clonal hematopoiesis of indeterminate potential among patients with a primary cancer and risk of second cancers.Leukemia · 2026Article
- Article
- Low-input proteomics identifies vWF as a negative regulator of Tet2 mutant hematopoietic stem cell expansion.Cell reports · 2026Article
- Enhancer-dependent gene regulation in space, time, and malignancies.International journal of cancer · 2026Review
- Silent, but not innocent: the emerging role of clonal hematopoiesis in predicting therapy-related myeloid neoplasms.Frontiers in oncology · 2026Review
- RNA modification systems as therapeutic targets.Nature reviews. Drug discovery · 2026Review
- Divergent molecular pathways drive monomorphic epitheliotropic and enteropathy-associated intestinal T-cell lymphoma.Leukemia · 2026Article
- Iron: Regulation, redox homeostasis, and ferroptosis in cancer.Ferroptosis and oxidative stress · 2026Article
- Targeting RUNX1 Germline Variants: Agents Under Investigation.Current hematologic malignancy reports · 2025Review
- Clonal hematopoiesis of indeterminate potential: a multisystem hub bridging hematopoietic dysfunction with non-hematopoietic diseases.Military Medical Research · 2025Review
- The TET protein family interactor PROSER1 sustains hematopoietic stem cell function.Blood advances · 2025Article
- Direct genetic transformation bypasses tumor-associated DNA methylation alterations.Genome biology · 2025Article
- Article
- Crosstalk between metabolism and epigenetics during macrophage polarization.Epigenetics & chromatin · 2025Review
- Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Somatic mutations and DNA methylation identify a subgroup of poor prognosis within lower-risk myelodysplastic syndromes.HemaSphere · 2025Article
- On correlative and causal links of replicative epimutations.Trends in genetics : TIG · 2025Review
122 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA methylation is tightly regulated throughout mammalian development, and altered DNA methylation patterns are a general hallmark of cancer. The methylcytosine dioxygenase TET2 is frequently mutated in hematological disorders, including acute myeloid leukemia (AML), and has been suggested to protect CG dinucleotide (CpG) islands and promoters from aberrant DNA methylation. In this study, we present a novel Tet2-dependent leukemia mouse model that closely recapitulates gene expression profiles and hallmarks of human AML1-ETO-induced AML. Using this model, we show that the primary effect of Tet2 loss in preleukemic hematopoietic cells is progressive and widespread DNA hypermethylation affecting up to 25% of active enhancer elements. In contrast, CpG island and promoter methylation does not change in a Tet2-dependent manner but increases relative to population doublings. We confirmed this specific enhancer hypermethylation phenotype in human AML patients with TET2 mutations. Analysis of immediate gene expression changes reveals rapid deregulation of a large number of genes implicated in tumorigenesis, including many down-regulated tumor suppressor genes. Hence, we propose that TET2 prevents leukemic transformation by protecting enhancers from aberrant DNA methylation and that it is the combined silencing of several tumor suppressor genes in TET2 mutated hematopoietic cells that contributes to increased stem cell proliferation and leukemogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.