ZFIN ID: ZDB-PUB-050201-7
Hematopoietic perturbation in zebrafish expressing a tel-jak2a fusion
Onnebo, S.M., Condron, M.M., McPhee, D.O., Lieschke, G.J., and Ward, A.C.
Date: 2005
Source: Experimental hematology   33(2): 182-188 (Journal)
Registered Authors: Lieschke, Graham J., McPhee, Dora, Ward, Alister C.
Keywords: none
MeSH Terms:
  • Acute Disease
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • DNA-Binding Proteins/genetics*
  • Disease Models, Animal
  • Embryo, Nonmammalian/physiology
  • Hematopoiesis/physiology*
  • Janus Kinase 2
  • Leukemia, Myeloid/genetics*
  • Peptide Fragments/chemistry
  • Protein-Tyrosine Kinases/genetics*
  • Proto-Oncogene Proteins/genetics*
  • Proto-Oncogene Proteins c-ets
  • Recombinant Fusion Proteins/metabolism
  • Repressor Proteins/genetics*
  • Zebrafish
PubMed: 15676212 Full text @ Exp. Hematol.
OBJECTIVE: Various TEL-JAK2 fusions have been identified in patients with lymphoblastic and myeloid leukemias that result in constitutive activation of the JAK2 kinase domain. Such fusions can mediate factor-independent growth of hematopoietic cell lines and induction of malignancy in mouse models. MATERIALS AND METHODS: To assess whether zebrafish could be utilized as a suitable model for the study of myeloid oncogenesis, we generated a zebrafish tel-jak2a fusion oncoprotein based on that seen in a case of chronic myeloid leukemia. This was transiently expressed in zebrafish embryos under the control of the spi1 promoter, which is strongly active in myeloid precursors. RESULTS: Visual, histological, and molecular analysis revealed disruption of normal embryonic hematopoiesis, including perturbation of the myeloid and erythroid lineages. CONCLUSION: These results indicate that the zebrafish tel-jak2a oncoprotein is functional, and suggest that this organism will be useful for the experimental study of myeloid malignancy.