PUBLICATION

c-myb hyperactivity leads to myeloid and lymphoid malignancies in zebrafish

Authors
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.
ID
ZDB-PUB-160728-15
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
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes