| Autor: |
Liu, W, Wu, M, Huang, Z, Lian, J, Chen, J, Wang, T, Leung, A Y H, Liao, Y, Zhang, Z, Liu, Q, Yen, K, Lin, S, Zon, L I, Wen, Z, Zhang, Y, Zhang, W |
| Zdroj: |
Leukemia; January 2017, Vol. 31 Issue: 1 p222-233, 12p |
| Abstrakt: |
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-gfptransgenic 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-mybtarget 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. |
| Databáze: |
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