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TET2 in Normal and Malignant Hematopoiesis
Abstract
The ten-eleven translocation (TET) family of enzymes were originally cloned from the translocation breakpoint of t(10;11) in infant acute myeloid leukemia (AML) with subsequent genomic analyses revealing somatic mutations and suppressed expression of TET family members across a range of malignancies, particularly enriched in hematological neoplasms. The TET family of enzymes is responsible for the hydroxylation of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), followed by active and passive mechanisms leading to DNA demethylation. Given the complexity and importance of DNA methylation events in cellular proliferation and differentiation, it comes as no surprise that the TET family of enzymes is intricately regulated by both small molecules and regulatory cooperating proteins. Here, we review the structure and function of TET2, its interactions with cooperating mutations and small molecules, and its role in aberrant hematopoiesis.
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“Mechanistically, DNMT3A catalyzes de novo DNA methylation whereas TET2 oxidizes methylated CpG to 5-hydroxymethyl cytosine (5-hmC) facilitating further modification to unmodified cysteine; mutations thus cause dysregulated DNA methylation and demethylation, respectively, altering the expression of genes involved in proliferation, differentiation and inflammation via chromatin-level changes 209,210”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [209]
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Belizaire, R., Wong, W. J., Robinette, M. L., & Ebert, B. L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00843-3 · Cited by 161
Metadata
- Authors
- Bowman, R. L., & Levine, R. L.
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-02-27
- Volume
- 7
- Issue
- 8
- Pages
- a026518
- ISSN
- 2157-1422
- Cited by
- 94
- References
- 73
- Language
- en
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 ›
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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.
