TET2 Inactivation Results in Pleiotropic Hematopoietic Abnormalities in Mouse and Is a Recurrent Event during Human Lymphomagenesis
Open accessAbstract
Loss-of-function mutations affecting one or both copies of the Ten-Eleven-translocation (TET)2 gene have been described in various human myeloid malignancies. We report that inactivation of Tet2 in mouse perturbs both early and late steps of hematopoiesis including myeloid and lymphoid differentiation in a cell-autonomous manner, endows the cells with competitive advantage, and eventually leads to the development of malignancies. We subsequently observed TET2 mutations in human lymphoid disorders. TET2 mutations could be detected in immature progenitors endowed with myeloid colony-forming potential. Our results show that the mutations present in lymphoid tumor cells may occur at both early and later steps of lymphoid development and indicate that impairment of TET2 function or/and expression predisposes to the development of hematological malignancies.
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Tet2 loss of function in murine HSPCs leads to increased self-renewal and pool expansion, higher competitive repopulation capacity, and a predisposition to hematological malignancy development.
“Indeed, Tet2 loss of function in murine HSPCs leads to increased self-renewal and pool expansion, higher competitive repopulation capacity, and a predisposition to hematological malignancy development.11, 12, 13”
From Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [13]
In BM chimeras, Tet2+/− PB CD45.2+ cells show increased repopulating capacity compared with WT in the PBS groups.
“As previously reported, we observed increased repopulating capacity in Tet2+/− PB CD45.2+ compared with WT in the PBS groups.11, 12, 13”
From Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [13]
Higher basal level of self-renewal, repopulation capacity, and general fitness is reported in Tet2 loss-of-function HSPCs.
“This likely results from a higher basal level of self-renewal, repopulation capacity, and general fitness reported in Tet2 loss-of-function HSPCs.11, 12, 13”
From Aging drives <i>Tet2</i> <i>+/−</i> clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [13]
D-2-hydroxyglutarate (D2HG) inhibits numerous demethylases, leading to changes in genomic and transcriptomic methylation profiles as well as gene expression and genome topology.
“D-2-hydroxyglutarate (D2HG) is one such oncometabolite, which inhibits numerous demethylases, leading to changes in genomic and transcriptomic methylation profiles as well as gene expression and genome topology 32,90-92 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [90]
This leads to significantly higher m6A levels in IDH1/2-mutant than in IDH1/2-wild-type AML, despite comparable FTO expression.
“This leads to significantly higher m6A levels in IDH1/2-mutant than in IDH1/2-wild-type AML, despite comparable FTO expression 90 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [90]
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Self-citation
- Authors
- Quivoron, C., Couronné, L., Della Valle, V., Lopez, C. K., Plo, I., Wagner-Ballon, O., Do Cruzeiro, M., Delhommeau, F., Arnulf, B., Stern, M.-H., Godley, L., Opolon, P., Tilly, H., Solary, E., Duffourd, Y., Dessen, P., Merle-Beral, H., Nguyen-Khac, F., Fontenay, M., Vainchenker, W., Bastard, C., Mercher, T., & Bernard, O. A.
- Affiliations
- Université Paris-Sud (FR)
- Hôpital Saint-Louis (FR)
- Inserm (FR)
- University of Chicago (US)
- Institut Gustave Roussy (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Bernard, Olivier A.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 20
- Issue
- 1
- Pages
- 25-38
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2028078153
- Cited by
- 924
- References
- 32
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 30 · 2023: 52 · 2022: 53 · 2021: 81 · 2020: 66 · 2019: 53 · 2018: 59 · 2017: 69 · 2016: 75 · 2015: 75 · 2014: 82 · 2013: 66 · 2012: 68
- FWCI
- 53.43
- Type
- journal article
- Language
- en
- Update notices
- erratum (2011-08-16)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 783 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ligue Contre le Cancer
- Institut National Du Cancer
- Fondation Gustave Roussy
- École des Neurosciences Paris Île de France
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- TET2, hematopoiesis, lymphoid differentiation, myeloid differentiation, lymphomagenesis, loss-of-function mutations, hematologic malignancies, myeloid progenitor cells, competitive advantage, mouse model
- MeSH terms
- Animals, DNA-Binding Proteins, Hematopoiesis, Hematopoietic Stem Cells, Homeostasis, Humans, Lymphoma, Mutation, Precancerous Conditions, Proto-Oncogene Proteins, Antigens, CD34, Cell Lineage, Gene Silencing, Myeloid Cells, Models, Animal, Dioxygenases, Mice
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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