Hematopoietic perturbation in zebrafish expressing a tel-jak2a fusion.
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.


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.


CONCLUSIONS
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.
Onnebo
Sara M N
SM
Centre for Cellular & Molecular Biology, School of Biological & Chemical Sciences, Deakin University, Burwood, Victoria, Australia.
Condron
Melanie M
MM
McPhee
Dora O
DO
Lieschke
Graham J
GJ
Ward
Alister C
AC
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000502:physiology; D006410:Hematopoiesis / Q000502:physiology*; D053614:Janus Kinase 2; D007951:Leukemia, Myeloid / Q000235:genetics*; D010446:Peptide Fragments / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D015027:Zebrafish; D000097764:ETS Translocation Variant 6 Protein
D004268:DNA-Binding Proteins; D053614:Janus Kinase 2; D010446:Peptide Fragments; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C507926:Jak2 protein, mouse