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.
Date: 2017
Source: Leukemia   31(1): 222-233 (Journal)
Registered Authors: Lian, Junwei, Wu, Mei, Zhang, Yiyue, Zon, Leonard I.
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Cycle/genetics
  • Cell Proliferation/genetics
  • Disease Models, Animal*
  • Hematopoietic Stem Cells/cytology
  • Humans
  • Leukemia, Myeloid, Acute/etiology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology*
  • Proto-Oncogene Proteins c-myb/metabolism*
  • Zebrafish
PubMed: 27457538 Full text @ Leukemia
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.