ZFIN ID: ZDB-PUB-160728-15
c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish
Liu, W., Wu, M., Huang, Z., Lian, J., Chen, J., Wang, T., Leung, A.Y., Liao, Y., Zhang, Z., Liu, Q., Yen, K., Lin, S., Zon, L.I., Wen, Z., Zhang, Y., Zhang, W.
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-myb(hyper)). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood. Strikingly, a small portion of c-myb(hyper) adult fish develops acute myeloid leukemia-like or acute lymphoid leukemia-like disorders with age. The myeloid and lymphoid malignancies in c-myb(hyper) 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-myb(hyper) 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.Leukemia advance online publication, 26 July 2016; doi:10.1038/leu.2016.170.