title: c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish.
abstract: The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-mybhyper). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood. Strikingly, a small portion of c-mybhyperadult fish develops acute myeloid leukemia-like or acute lymphoid leukemia-like disorders with age. The myeloid and lymphoid malignancies in c-mybhyperadult fish are likely caused by the hyperactivity of c-myb, resulting in the dysregulation of a number of cell-cycle-related genes and hyperproliferation of hematopoietic precursor cells. Finally, treatment with c-myb target drug flavopiridol can relieve the MDS-like symptoms in both c-mybhyperembryos and adult fish. Our study establishes a zebrafish model for studying the cellular and molecular mechanisms underlying c-Myb-associated leukemogenesis as well as for anti-leukemic drug screening.
authors.affiliation: State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Lian
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Division of Haematology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: A Y H
authors.initials: AY
authors.lastname: Leung
authors.affiliation: State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.|Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.|Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Haematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: K
authors.initials: K
authors.lastname: Yen
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lin
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Children's Hospital, and Dana Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: L I
authors.initials: LI
authors.lastname: Zon
authors.affiliation: State Key Laboratory of Molecular Neuroscience, Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China.|Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology*; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D020598:Proto-Oncogene Proteins c-myb