PUBLICATION
Development of BCR-ABL1 Transgenic Zebrafish Model Reproducing Chronic Myeloid Leukemia (CML) Like-Disease and Providing a New Insight into CML Mechanisms
- Authors
- Zizioli, D., Bernardi, S., Varinelli, M., Farina, M., Mignani, L., Bosio, K., Finazzi, D., Monti, E., Polverelli, N., Malagola, M., Borsani, E., Borsani, G., Russo, D.
- ID
- ZDB-PUB-210307-7
- Date
- 2021
- Source
- Cells 10(2): (Journal)
- Registered Authors
- Borsani, Giuseppe
- Keywords
- BCR-ABL1, UAS/hsp70-Gal4, chronic myeloid leukemia (CML), embryonic development, hematopoiesis, transgenic animal model, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Disease Models, Animal
- Humans
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics*
- Zebrafish
- PubMed
- 33669758 Full text @ Cells
Citation
Zizioli, D., Bernardi, S., Varinelli, M., Farina, M., Mignani, L., Bosio, K., Finazzi, D., Monti, E., Polverelli, N., Malagola, M., Borsani, E., Borsani, G., Russo, D. (2021) Development of BCR-ABL1 Transgenic Zebrafish Model Reproducing Chronic Myeloid Leukemia (CML) Like-Disease and Providing a New Insight into CML Mechanisms. Cells. 10(2):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping