Hematopoietic perturbation in zebrafish expressing a tel-jak2a fusion

Exp Hematol. 2005 Feb;33(2):182-8. doi: 10.1016/j.exphem.2004.10.019.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

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

Substances

  • DNA-Binding Proteins
  • ETS translocation variant 6 protein
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Protein-Tyrosine Kinases
  • Jak2 protein, mouse
  • Janus Kinase 2