ArticleLeukemia2016
DNMT3A(R882H) mutant and Tet2 inactivation cooperate in the deregulation of DNA methylation control to induce lymphoid malignancies in mice.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
- Review
- Clones in blood and stratified epithelial cells, and their drivers.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- Advancing the understanding and management of angioimmunoblastic T-cell lymphoma: insights into its pathogenesis, clinical features, and emerging therapeutic strategies.Frontiers in oncology · 2025Review
- The dark side of stemness - the role of hematopoietic stem cells in development of blood malignancies.Frontiers in oncology · 2024Review
- Advances in the pathogenesis and therapeutic strategies of angioimmunoblastic T-cell lymphoma.Clinical and experimental medicine · 2023Review
- DNMT3AOncogene · 2023Article
- Mature T-cell and NK-cell lymphomas: updates on molecular genetic features.International journal of hematology · 2023Review
- Epigenetic Modification of Cytosines in Hematopoietic Differentiation and Malignant Transformation.International journal of molecular sciences · 2023Review
- The implication of next-generation sequencing in the diagnosis and clinical management of non-Hodgkin lymphomas.Frontiers in oncology · 2023Review
- TargetingCancers · 2022Review
- Role of TET dioxygenases in the regulation of both normal and pathological hematopoiesis.Journal of experimental & clinical cancer research : CR · 2022Review
- Review
- Review
- Targeting the T-Cell Lymphoma Epigenome Induces Cell Death, Cancer Testes Antigens, Immune-Modulatory Signaling Pathways.Molecular cancer therapeutics · 2021Article
- Biology and Molecular Pathogenesis of Mature T-Cell Lymphomas.Cold Spring Harbor perspectives in medicine · 2021Review
- Alterations toCancer research · 2021Review
- TET2: A cornerstone in normal and malignant hematopoiesis.Cancer science · 2021Review
- Update on recurrent mutations in angioimmunoblastic T-cell lymphoma.International journal of clinical and experimental pathology · 2021Review
- Deciphering the Complexity of 3D Chromatin Organization Driving Lymphopoiesis and Lymphoid Malignancies.Frontiers in immunology · 2021Review
- Review
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
TEN-ELEVEN-TRANSLOCATION-2 (TET2) and DNA-METHYLTRANSFERASE-3A (DNMT3A), both encoding proteins involved in regulating DNA methylation, are mutated in hematological malignancies affecting both myeloid and lymphoid lineages. We previously reported an association of TET2 and DNMT3A mutations in progenitors of patients with angioimmunoblastic T-cell lymphomas (AITL). Here, we report on the cooperative effect of Tet2 inactivation and DNMT3A mutation affecting arginine 882 (DNMT3A(R882H)) using a murine bone marrow transplantation assay. Five out of eighteen primary recipients developed hematological malignancies with one mouse developing an AITL-like disease, two mice presenting acute myeloid leukemia (AML)-like and two others T-cell acute lymphoblastic leukemia (T-ALL)-like diseases within 6 months following transplantation. Serial transplantations of DNMT3A(R882H) Tet2(-/-) progenitors led to a differentiation bias toward the T-cell compartment, eventually leading to AITL-like disease in 9/12 serially transplanted recipients. Expression profiling suggested that DNMT3A(R882H) Tet2(-/-) T-ALLs resemble those of NOTCH1 mutant. Methylation analysis of DNMT3A(R882H) Tet2(-/-) T-ALLs showed a global increase in DNA methylation affecting tumor suppressor genes and local hypomethylation affecting genes involved in the Notch pathway. Our data confirm the transformation potential of DNMT3A(R882H) Tet2(-/-) progenitors and represent the first cooperative model in mice involving Tet2 inactivation driving lymphoid malignancies.
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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.