ArticleProceedings of the National Academy of Sciences of the United States of America2015
Disregulated expression of the transcription factor ThPOK during T-cell development leads to high incidence of T-cell lymphomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Super-enhancer profiling reveals ThPOK/ZBTB7B, a CD4Cellular and molecular life sciences : CMLS · 2025Article
- Zbtb7b defines a compensatory mechanism in MASLD-related HCC progression by suppressing H19-mediated hepatic lipid deposition.Physiological reports · 2024Article
- ThPOK is a critical multifaceted regulator of myeloid lineage development.Nature immunology · 2023Article
- Epigenetic DNA methylation of Zbtb7b regulates the population of double-positive CD4Journal of translational medicine · 2022Article
- NuRD complex recruitment to Thpok mediates CD4Science immunology · 2022Article
- ThPOK inhibits the immune escape of gastric cancer cells by inducing STPG1 to inactivate the ERK pathway.BMC immunology · 2022Article
- Article
- ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells.Frontiers in immunology · 2021Review
- Vertebrate GAF/ThPOK: emerging functions in chromatin architecture and transcriptional regulation.Cellular and molecular life sciences : CMLS · 2018Review
- Expression of Master Regulators of T-cell, Helper T-cell and Follicular Helper T-cell Differentiation in Angioimmunoblastic T-cell Lymphoma.Internal medicine (Tokyo, Japan) · 2017Article
- Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes.Nature communications · 2017Article
- BET bromodomain-mediated interaction between ERG and BRD4 promotes prostate cancer cell invasion.Oncotarget · 2016Article
- Article
- PRDM14 promotes RAG-dependent Notch1 driver mutations in mouse T-ALL.Biology open · 2016Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor T-helper-inducing POZ/Krueppel-like factor (ThPOK, encoded by the Zbtb7b gene) plays widespread and critical roles in T-cell development, particularly as the master regulator of CD4 commitment. Here we show that mice expressing a constitutive T-cell-specific ThPOK transgene (ThPOK(const) mice) develop thymic lymphomas. These tumors resemble human T-cell acute lymphoblastic leukemia (T-ALL), in that they predominantly exhibit activating Notch1 mutations. Lymphomagenesis is prevented if thymocyte development is arrested at the DN3 stage by recombination-activating gene (RAG) deficiency, but restored by introduction of a T-cell receptor (TCR) transgene or by a single injection of anti-αβTCR antibody into ThPOK(const) RAG-deficient mice, which promotes development to the CD4(+)8(+) (DP) stage. Hence, TCR signals and/or traversal of the DN (double negative) > DP (double positive) checkpoint are required for ThPOK-mediated lymphomagenesis. These results demonstrate a novel link between ThPOK, TCR signaling, and lymphomagenesis. Finally, we present evidence that ectopic ThPOK expression gives rise to a preleukemic and self-perpetuating DN4 lymphoma precursor population. Our results collectively define a novel role for ThPOK as an oncogene and precisely map the stage in thymopoiesis susceptible to ThPOK-dependent tumor initiation.
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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.