Development of BCR-ABL1 Transgenic Zebrafish Model Reproducing Chronic Myeloid Leukemia (CML) Like-Disease and Providing a New Insight into CML Mechanisms
Daniela Zizioli,
Simona Bernardi,
Marco Varinelli,
Mirko Farina,
Luca Mignani,
Katia Bosio,
Dario Finazzi,
Eugenio Monti,
Nicola Polverelli,
Michele Malagola,
Elisa Borsani,
Giuseppe Borsani,
Domenico Russo
Affiliations
Daniela Zizioli
Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Simona Bernardi
Unit of Hematology, Department of Clinical and Experimental Sciences, University of Brescia, Bone Marrow Transplant Unit, ASST Spedali Civili, 25123 Brescia, Italy
Marco Varinelli
Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Mirko Farina
Unit of Hematology, Department of Clinical and Experimental Sciences, University of Brescia, Bone Marrow Transplant Unit, ASST Spedali Civili, 25123 Brescia, Italy
Luca Mignani
Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Katia Bosio
Unit of Hematology, Department of Clinical and Experimental Sciences, University of Brescia, Bone Marrow Transplant Unit, ASST Spedali Civili, 25123 Brescia, Italy
Dario Finazzi
Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Eugenio Monti
Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Nicola Polverelli
Unit of Hematology, Department of Clinical and Experimental Sciences, University of Brescia, Bone Marrow Transplant Unit, ASST Spedali Civili, 25123 Brescia, Italy
Michele Malagola
Unit of Hematology, Department of Clinical and Experimental Sciences, University of Brescia, Bone Marrow Transplant Unit, ASST Spedali Civili, 25123 Brescia, Italy
Elisa Borsani
Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
Giuseppe Borsani
Unit of Biology and Genetic, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Domenico Russo
Unit of Hematology, Department of Clinical and Experimental Sciences, University of Brescia, Bone Marrow Transplant Unit, ASST Spedali Civili, 25123 Brescia, Italy
Zebrafish has proven to be a versatile and reliable experimental in vivo tool to study human hematopoiesis and model hematological malignancies. Transgenic technologies enable the generation of specific leukemia types by the expression of human oncogenes under specific promoters. Using this technology, a variety of myeloid and lymphoid malignancies zebrafish models have been described. Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the BCR-ABL1 fusion gene, derived from the t (9;22) translocation causing the Philadelphia Chromosome (Ph). The BCR-ABL1 protein is a constitutively activated tyrosine kinas inducing the leukemogenesis and resulting in an accumulation of immature leukemic cells into bone marrow and peripheral blood. To model Ph+ CML, a transgenic zebrafish line expressing the human BCR-ABL1 was generated by the Gal4/UAS system, and then crossed with the hsp70-Gal4 transgenic line. The new line named (BCR-ABL1pUAS:CFP/hsp70-Gal4), presented altered expression of hematopoietic markers during embryonic development compared to controls and transgenic larvae showed proliferating hematopoietic cells in the caudal hematopoietic tissue (CHT). The present transgenic zebrafish would be a robust CML model and a high-throughput drug screening tool.
