ArticleThe Journal of clinical investigation2009
The TEL-AML1 leukemia fusion gene dysregulates the TGF-beta pathway in early B lineage progenitor cells.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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Who cites it
73 citing papers in PubMed, 110 citations in OpenAlex.
- The risks of delay?Haematologica · 2026Article
- Timing of microbial exposure and risk of infection-promoted acute lymphoblastic leukemia.Haematologica · 2026Article
- BCR-ABL1 Drives Transcriptional Reprogramming of Chronic Myeloid Leukemia Cells for Immune Evasion Through C/EBPβ.MedComm · 2026Article
- Deletion of 9p drives B-ALL through heterozygous inactivation of Pax5 and Cd72 in preleukemic cells.JCI insight · 2026Article
- Targeting oncogene-induced senescence in ETV6::RUNX1 pre-leukemic cells.Cell death discovery · 2026Article
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia.HemaSphere · 2025Article
- Comparative Profiling of Regulatory Modules as a Tool for Identifying the Transcription Factor Network Linked to Leukemogenesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Impact of genetic alterations on central nervous system progression of primary vitreoretinal lymphoma.Haematologica · 2024Article
- Identification of Gene Regulatory Networks in B-Cell Progenitor Differentiation and Leukemia.Genes · 2024Article
- SPAG6 regulates cell proliferation and apoptosis via TGF-β/Smad signal pathway in adult B-cell acute lymphoblastic leukemia.International journal of hematology · 2024Article
- Inflammation as a driver of hematological malignancies.Frontiers in oncology · 2024Review
- The Diverse Roles of ETV6 Alterations in B-Lymphoblastic Leukemia and Other Hematopoietic Cancers.Advances in experimental medicine and biology · 2024Review
- Age and ligand specificity influence the outcome of pathogen engagement on preleukemic and leukemic B-cell precursor populations.Blood advances · 2023Article
- Functional Characterization of Transforming Growth Factor-β Signaling in Dasatinib Resistance and Pre-BCRCancers · 2023Article
- Immune stress suppresses innate immune signaling in preleukemic precursor B-cells to provoke leukemia in predisposed mice.Nature communications · 2023Article
- Cytokine Hyperresponsiveness in Children With ETV6::RUNX1-positive Acute Lymphoblastic Leukemia After Challenge With Common Pathogens.HemaSphere · 2023Article
- The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia.Frontiers in oncology · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Chromosome translocation to generate the TEL-AML1 (also known as ETV6-RUNX1) chimeric fusion gene is a frequent and early or initiating event in childhood acute lymphoblastic leukemia (ALL). Our starting hypothesis was that the TEL-AML1 protein generates and maintains preleukemic clones and that conversion to overt disease requires secondary genetic changes, possibly in the context of abnormal immune responses. Here, we show that a murine B cell progenitor cell line expressing inducible TEL-AML1 proliferates at a slower rate than parent cells but is more resistant to further inhibition of proliferation by TGF-beta. This facilitates the competitive expansion of TEL-AML1-expressing cells in the presence of TGF-beta. Further analysis indicated that TEL-AML1 binds to a principal TGF-beta signaling target, Smad3, and compromises its ability to activate target promoters. In mice expressing a TEL-AML1 transgene, early, pre-pro-B cells were increased in number and also showed reduced sensitivity to TGF-beta-mediated inhibition of proliferation. Moreover, expression of TEL-AML1 in human cord blood progenitor cells led to the expansion of a candidate preleukemic stem cell population that had an early B lineage phenotype (CD34+CD38-CD19+) and a marked growth advantage in the presence of TGF-beta. Collectively, these data suggest a plausible mechanism by which dysregulated immune responses to infection might promote the malignant evolution of TEL-AML1-expressing preleukemic clones.
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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.