ArticleLeukemia2015
Epigenetic therapy restores normal hematopoiesis in a zebrafish model of NUP98-HOXA9-induced myeloid disease.
Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- DNA Methylation Dynamics in Development and Disease: Insights from Zebrafish Models.Biomedicines · 2026Review
- Myeloid Targeted Human MLL-ENL and MLL-AF9 Induces cdk9 and bcl2 Expression in Zebrafish Embryos.PLoS genetics · 2024Article
- Traditional Chinese medicine for acute myelocytic leukemia therapy: exploiting epigenetic targets.Frontiers in pharmacology · 2024Review
- Article
- One Host-Multiple Applications: Zebrafish (International journal of molecular sciences · 2022Review
- Zebrafish models of inflammation in hematopoietic development and disease.Frontiers in cell and developmental biology · 2022Review
- Zebrafish models of acute leukemias: Current models and future directions.Wiley interdisciplinary reviews. Developmental biology · 2021Review
- Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?Biology open · 2021Article
- Biomechanical Regulation of Hematopoietic Stem Cells in the Developing Embryo.Current tissue microenvironment reports · 2021Article
- [Myelodysplastic syndrome with t(7;11)(p15;p15)/NHA9: 2 cases report and lectures review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2020Review
- Design of a Comprehensive Fluorescence in Situ Hybridization Assay for Genetic Classification of T-Cell Acute Lymphoblastic Leukemia.The Journal of molecular diagnostics : JMD · 2020Article
- Zebrafish Models of Cancer-New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate.Genes · 2019Review
- Modeling hematopoietic disorders in zebrafish.Disease models & mechanisms · 2019Review
- The zebrafish: A fintastic model for hematopoietic development and disease.Wiley interdisciplinary reviews. Developmental biology · 2018Review
- Genetic Models of Leukemia in Zebrafish.Frontiers in cell and developmental biology · 2018Review
- Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish.BioMed research international · 2018Article
- The molecular pathogenesis of the NUP98-HOXA9 fusion protein in acute myeloid leukemia.Leukemia · 2017Article
- Clinical implications of genome-wide DNA methylation studies in acute myeloid leukemia.Journal of hematology & oncology · 2017Review
- Modeling Myeloid Malignancies Using Zebrafish.Frontiers in oncology · 2017Review
- Review
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 3 countries.
Funding
Abstract
Acute myeloid leukemia (AML) occurs when multiple genetic aberrations alter white blood cell development, leading to hyperproliferation and arrest of cell differentiation. Pertinent animal models link in vitro studies with the use of new agents in clinical trials. We generated a transgenic zebrafish expressing human NUP98-HOXA9 (NHA9), a fusion oncogene found in high-risk AML. Embryos developed a preleukemic state with anemia and myeloid cell expansion, and adult fish developed a myeloproliferative neoplasm (MPN). We leveraged this model to show that NHA9 increases the number of hematopoietic stem cells, and that oncogenic function of NHA9 depends on downstream activation of meis1, the PTGS/COX pathway and genome hypermethylation through the DNA methyltransferase, dnmt1. We restored normal hematopoiesis in NHA9 embryos with knockdown of meis1 or dnmt1, as well as pharmacologic treatment with DNA (cytosine-5)-methyltransferase (DNMT) inhibitors or cyclo-oxygenase (COX) inhibitors. DNMT inhibitors reduced genome methylation to near normal levels. Strikingly, we discovered synergy when we combined sub-monotherapeutic doses of a histone deacetylase inhibitor plus either a DNMT inhibitor or COX inhibitor to block the effects of NHA9 on zebrafish blood development. Our work proposes novel drug targets in NHA9-induced myeloid disease, and suggests rational therapies by combining minimal doses of known bioactive compounds.
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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.