ArticleThe Journal of experimental medicine2010
NKX3.1 is a direct TAL1 target gene that mediates proliferation of TAL1-expressing human T cell acute lymphoblastic leukemia.
Article in The Journal of experimental medicine, 2010. 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, 69 citations in OpenAlex.
- TCRα rearrangements identify a subgroup of NKL-deregulated adult T-ALLs associated with favorable outcome.Leukemia · 2018Trial
- The spectrum of immunoglobulin heavy chain enhancer hijacking in chronic lymphocytic leukemia.Leukemia · 2026Article
- Identification of microprotein-coding intronic polyadenylation isoforms and function in genotoxic anticancer drug response.Genome biology · 2025Article
- Super-Enhancer-Driven IRF2BP2 is Activated by Master Transcription Factors and Sustains T-ALL Cell Growth and Survival.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulatory mechanisms and context-dependent roles of TAL1 in T-cell acute lymphoblastic leukemia.Haematologica · 2024Article
- Targeting dual oncogenic machineries driven by TAL1 and PI3K-AKT pathways in T-cell acute lymphoblastic leukemia.Haematologica · 2023Article
- T cell receptor and IL-2 signaling strength control memory CD8Nature communications · 2022Article
- Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 inFrontiers in immunology · 2022Article
- The Role of NKL Homeobox Genes in T-Cell Malignancies.Biomedicines · 2021Review
- Review
- A narrative review of the roles of muscle segment homeobox transcription factor family in cancer.Annals of translational medicine · 2021Review
- NKL-Code in Normal and Aberrant Hematopoiesis.Cancers · 2021Review
- The transcription factor TAL1 and miR-17-92 create a regulatory loop in hematopoiesis.Scientific reports · 2020Article
- Ldb1 is required for Lmo2 oncogene-induced thymocyte self-renewal and T-cell acute lymphoblastic leukemia.Blood · 2020Article
- The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia.Cold Spring Harbor perspectives in medicine · 2020Review
- Deregulated NKL Homeobox Genes in B-Cell Lymphoma.Cancers · 2019Review
- LMO2 activation by deacetylation is indispensable for hematopoiesis and T-ALL leukemogenesis.Blood · 2019Article
- Deregulated expression of NKL homeobox genes in T-cell lymphomas.Oncotarget · 2019Article
- Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia.International journal of hematology · 2019Review
- Nkx2-3-A Slippery Slope From Development Through Inflammation Toward Hematopoietic Malignancies.Biomarker insights · 2018Review
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TAL1 (also known as SCL) is expressed in >40% of human T cell acute lymphoblastic leukemias (T-ALLs). TAL1 encodes a basic helix-loop-helix transcription factor that can interfere with the transcriptional activity of E2A and HEB during T cell leukemogenesis; however, the oncogenic pathways directly activated by TAL1 are not characterized. In this study, we show that, in human TAL1-expressing T-ALL cell lines, TAL1 directly activates NKX3.1, a tumor suppressor gene required for prostate stem cell maintenance. In human T-ALL cell lines, NKX3.1 gene activation is mediated by a TAL1-LMO-Ldb1 complex that is recruited by GATA-3 bound to an NKX3.1 gene promoter regulatory sequence. TAL1-induced NKX3.1 activation is associated with suppression of HP1-α (heterochromatin protein 1 α) binding and opening of chromatin on the NKX3.1 gene promoter. NKX3.1 is necessary for T-ALL proliferation, can partially restore proliferation in TAL1 knockdown cells, and directly regulates miR-17-92. In primary human TAL1-expressing leukemic cells, the NKX3.1 gene is expressed independently of the Notch pathway, and its inactivation impairs proliferation. Finally, TAL1 or NKX3.1 knockdown abrogates the ability of human T-ALL cells to efficiently induce leukemia development in mice. These results suggest that tumor suppressor or oncogenic activity of NKX3.1 depends on tissue expression.
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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.