ArticleBlood2014
Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
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- Development of Epigenetic Modifiers with Therapeutic Potential in FMS-Related Tyrosine Kinase 3/Internal Tandem Duplication (FLT3/ITD) Acute Myeloid Leukemia and Other Blood Malignancies.ACS pharmacology & translational science · 2024Article
- Myeloid Targeted Human MLL-ENL and MLL-AF9 Induces cdk9 and bcl2 Expression in Zebrafish Embryos.PLoS genetics · 2024Article
- ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD.Molecular oncology · 2023Article
- Zebrafish-based platform for emerging bio-contaminants and virus inactivation research.The Science of the total environment · 2023Review
- Learning from Zebrafish Hematopoiesis.Advances in experimental medicine and biology · 2023Review
- Pivotal role of cytosolic phospholipase PLA2G4A in the pathogenesis ofGenes & diseases · 2023Article
- Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish.The Journal of experimental medicine · 2022Article
- Evolution and Potential Subfunctionalization of DuplicatedJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- The Zebrafish model in dermatology: an update for clinicians.Discover oncology · 2022Review
- Zebrafish models of acute leukemias: Current models and future directions.Wiley interdisciplinary reviews. Developmental biology · 2021Review
- Dhx15 regulates zebrafish definitive hematopoiesis through the unfolded protein response pathway.Cancer science · 2021Article
- Selectively targeting FLT3-ITD mutants over FLT3-wt by a novel inhibitor for acute myeloid leukemia.Haematologica · 2021Article
- Molecular and genomic landscapes in secondary & therapy related acute myeloid leukemia.American journal of blood research · 2021Review
- Characterization of somatic mutation-associated microenvironment signatures in acute myeloid leukemia patients based on TCGA analysis.Scientific reports · 2020Article
- Article
- Pediatric Cancer Models in Zebrafish.Trends in cancer · 2020Review
- Follistatin is a novel therapeutic target and biomarker in FLT3/ITD acute myeloid leukemia.EMBO molecular medicine · 2020Article
- Zebrafish Models of Cancer-New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate.Genes · 2019Review
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
FMS-like tyrosine kinase 3 (FLT3) is expressed in human hematopoietic stem and progenitor cells (HSPCs) but its role during embryogenesis is unclear. In acute myeloid leukemia (AML), internal tandem duplication (ITD) of FLT3 at the juxtamembrane (JMD) and tyrosine kinase (TKD) domains (FLT3-ITD(+)) occurs in 30% of patients and is associated with inferior clinical prognosis. TKD mutations (FLT3-TKD(+)) occur in 5% of cases. We made use of zebrafish to examine the role of flt3 in developmental hematopoiesis and model human FLT3-ITD(+) and FLT3-TKD(+) AML. Zebrafish flt3 JMD and TKD were remarkably similar to their mammalian orthologs. Morpholino knockdown significantly reduced the expression of l-plastin (pan-leukocyte), csf1r, and mpeg1 (macrophage) as well as that of c-myb (definitive HSPCs), lck, and rag1 (T-lymphocyte). Expressing human FLT3-ITD in zebrafish embryos resulted in expansion and clustering of myeloid cells (pu.1(+), mpo(+), and cebpα(+)) which were ameliorated by AC220 and associated with stat5, erk1/2, and akt phosphorylation. Human FLT3-TKD (D835Y) induced significant, albeit modest, myeloid expansion resistant to AC220. This study provides novel insight into the role of flt3 during hematopoiesis and establishes a zebrafish model of FLT3-ITD(+) and FLT3-TKD(+) AML that may facilitate high-throughput screening of novel and personalized agents.
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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.