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Animal Models

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-mybhyper adult fish develops acute myeloid leukemia-like or acute lymphoid leukemia-like disorders with age. The myeloid and lymphoid malignancies in c-mybhyper adult 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-mybhyper embryos 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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81470335, 81200340 and 31229003), The Ministry of Science and Technology Project 863 (SS2015AA020309), Team Program of Guangdong Natural Science Foundation (2014A030312002), Talent Recruitment funding and Excellent Young Teacher funding (Yq2013025) of Guangdong Higher Education Institutes and Peal River S&T Nova Program of Guangzhou (2013J2200032).

Author contributions

WL, MW and ZH designed the research, performed most of the experiments and analyzed the data. JL, JC and TW performed some experiments. AYHL, YL, ZZ, QL, KY, SL and LIZ designed some experiments and revised the manuscript. WL, ZW, YZ and WZ designed the research, analyzed the data and prepared the manuscript.

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Correspondence to Y Zhang or W Zhang.

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Liu, W., Wu, M., Huang, Z. et al. c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish. Leukemia 31, 222–233 (2017). https://doi.org/10.1038/leu.2016.170

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