ArticleBlood cancer discovery2022
The Cell Type-Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and TET2-Mutant Preleukemia.
Article in Blood cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.Stem cell reviews and reports · 2026Review
- Mechanisms of Thrombocytosis in Iron-Deficiency Anemia.European journal of haematology · 2026Review
- Prognostic Significance of Cell-Free DNA Derived 5-Hydroxymethylcytosine Signatures in Newly Diagnosed Multiple Myeloma.JCO precision oncology · 2026Article
- Clonal hematopoiesis of indeterminate potential (CHIP)-a pivotal contributor of aging and related disorders.Annals of translational medicine · 2026Review
- Novel and emerging therapeutic strategies for clonal hematopoiesis.Haematologica · 2026Review
- Human TET2-Mutant Clonal Hematopoiesis Expansion Is Driven by Distinct Inflammatory Signaling Responses in Stem Cells Versus Myeloid Progeny.Blood cancer discovery · 2026Article
- DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency.Cancer discovery · 2026Article
- A 5-hydroxymethylcytosine-based noninvasive model for acute myocardial infarction in type 2 diabetes: implications in cardiovascular outcomes from a 5-year median follow-up study.Cardiovascular diabetology · 2026Article
- Curcuminoids Activate TET Enzymes and Increase DNA Hydroxymethylation and Active Demethylation in Leukemia Cells.International journal of molecular sciences · 2025Article
- Vitamin C enhances cisplatin sensitivity in bladder cancer via 5hmC-mediated epigenetic modulation of ATF4.Clinical epigenetics · 2025Article
- 5-hydroxymethylcytosine analysis reveals stable epigenomic changes in tumor tissue that enable cancer detection in cell-free DNA.Communications biology · 2025Article
- A single-cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis.Cell reports · 2025Article
- Article
- The incidence, risk factors, and survival of acute myeloid leukemia secondary to chronic myelomonocytic leukemia: a population-based study.Translational cancer research · 2025Article
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- Discrete genetic subtypes and tumor microenvironment signatures correlate with peripheral T-cell lymphoma outcomes.Leukemia · 2025Article
- The physiological functions of ascorbate in the development of cancer.Disease models & mechanisms · 2025Review
- TET2 deficiency increases the competitive advantage of hematopoietic stem and progenitor cells through upregulation of thrombopoietin receptor signaling.Nature communications · 2025Article
- Article
- TET2 mutation in acute myeloid leukemia: biology, clinical significance, and therapeutic insights.Clinical epigenetics · 2024Review
Corrections and comments
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Authors and funding
25 authors at 3 institutions in 5 countries.
Funding
Abstract
The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that is mediated by ten-eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape of normal hematopoiesis and identify cell type-specific 5hmC profiles associated with active transcription and chromatin accessibility of key hematopoietic regulators. We utilized CRISPR/Cas9 to model TET2 loss-of-function mutations in primary human hematopoietic stem and progenitor cells (HSPC). Disrupted cells exhibited increased colonies in serial replating, defective erythroid/megakaryocytic differentiation, and in vivo competitive advantage and myeloid skewing coupled with reduction of 5hmC at erythroid-associated gene loci. Azacitidine and ascorbate restored 5hmC abundance and slowed or reverted the expansion of TET2-mutant clones in vivo. These results demonstrate the key role of 5hmC in normal hematopoiesis and TET2-mutant phenotypes and raise the possibility of utilizing these agents to further our understanding of preleukemia and clonal hematopoiesis. SIGNIFICANCE: We show that 5-hydroxymethylation profiles are cell type-specific and associated with transcriptional abundance and chromatin accessibility across human hematopoiesis. TET2 loss caused aberrant growth and differentiation phenotypes and disrupted 5hmC and transcriptional landscapes. Treatment of TET2 KO HSPCs with ascorbate or azacitidine reverted 5hmC profiles and restored aberrant phenotypes. This article is highlighted in the In This Issue feature, p. 265.
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