ArticleLeukemia2012
Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 75 citations in OpenAlex.
- Article
- Altered thymic niche synergistically drives the massive proliferation of malignant thymocytes.eLife · 2025Article
- Transient Differentiation-State Plasticity Occurs during Acute Lymphoblastic Leukemia Initiation.Cancer research · 2024Article
- Case report: Rare case of donor cell-derived T-cell acute lymphoblastic leukaemia in a female patient after receiving an allo-transplant from her male sibling.British journal of haematology · 2023Article
- Learning from Zebrafish Hematopoiesis.Advances in experimental medicine and biology · 2023Review
- Therapeutic targeting of LCK tyrosine kinase and mTOR signaling in T-cell acute lymphoblastic leukemia.Blood · 2022Article
- Article
- IRF4 drives clonal evolution and lineage choice in a zebrafish model of T-cell lymphoma.Nature communications · 2022Article
- Zebrafish models of acute leukemias: Current models and future directions.Wiley interdisciplinary reviews. Developmental biology · 2021Review
- PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis.Leukemia · 2021Article
- Benefits of Zebrafish Xenograft Models in Cancer Research.Frontiers in cell and developmental biology · 2021Review
- Pediatric Cancer Models in Zebrafish.Trends in cancer · 2020Review
- Article
- Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) drives migration and progression of T-cell acute lymphoblastic leukemia in vitro and in vivo.Oncogenesis · 2020Article
- Tackling Acute Lymphoblastic Leukemia-One Fish at a Time.International journal of molecular sciences · 2019Review
- Modeling hematopoietic disorders in zebrafish.Disease models & mechanisms · 2019Review
- Zebrafish and Medaka: Two Teleost Models of T-Cell and Thymic Development.International journal of molecular sciences · 2019Review
- The side population enriches for leukemia-propagating cell activity and Wnt pathway expression in zebrafish acute lymphoblastic leukemia.Haematologica · 2019Article
- Article
- Semisynthetic aurones inhibit tubulin polymerization at the colchicine-binding site and repress PC-3 tumor xenografts in nude mice and myc-induced T-ALL in zebrafish.Scientific reports · 2019Article
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
NOTCH1 pathway activation contributes to the pathogenesis of over 60% of T-cell acute lymphoblastic leukemia (T-ALL). While Notch is thought to exert the majority of its effects through transcriptional activation of Myc, it also likely has independent roles in T-ALL malignancy. Here, we utilized a zebrafish transgenic model of T-ALL, where Notch does not induce Myc transcription, to identify a novel Notch gene expression signature that is also found in human T-ALL and is regulated independently of Myc. Cross-species microarray comparisons between zebrafish and mammalian disease identified a common T-ALL gene signature, suggesting that conserved genetic pathways underlie T-ALL development. Functionally, Notch expression induced a significant expansion of pre-leukemic clones; however, a majority of these clones were not fully transformed and could not induce leukemia when transplanted into recipient animals. Limiting-dilution cell transplantation revealed that Notch signaling does not increase the overall frequency of leukemia-propagating cells (LPCs), either alone or in collaboration with Myc. Taken together, these data indicate that a primary role of Notch signaling in T-ALL is to expand a population of pre-malignant thymocytes, of which a subset acquire the necessary mutations to become fully transformed LPCs.
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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.