Zebrafish Acute Myeloid Leukemia Models

Acute myeloid leukemia (AML) is a heterogeneous disease comprising a broad spectrum of genetic mutations with loss and gain of functional phenotype that can be acquired in childhood or adulthood, the nature of the mutation and timing of onset affect this heterogeneous group Cancer prognosis. The diversity of these different cancers underscores the need to develop more targeted and personalized therapeutic interventions. To achieve this, there is therefore a need to develop better model organisms that recapitulate the specific mutations and phenotypes of these diseases.

Hematopoietic regulation at the molecular level is highly conserved between zebrafish and humans, with more than 80% of disease-causing human proteins having orthologs in zebrafish. Zebrafish have several distinctive features that make them attractive as model systems, such as their relatively inexpensive maintenance, external development, and ease of genetic manipulation. Furthermore, in the early stages of its development, the zebrafish is translucent, allowing direct observation of different cells and tissues in real time. Therefore, zebrafish are well suited to study dynamic processes such as hematopoietic development and homeostasis.

Fig.1 The benefits of zebrafish in leukemia research.

Our Zebrafish AML Models

Creative Biogene has more than ten years of experience in zebrafish disease research, and we have a wealth of zebrafish models and genome editing platforms. We can achieve mutagenesis in a number of ways, including through the use of chemicals, radiation, viral vectors and more targeted approaches such as Cas9/CRISPR, Targeted Local Lesions Induced in Genomes (TILLING), zinc finger nucleases, or transcription activator-responsive nuclease (TALEN)-mediated gene editing. We can provide stable transgenic zebrafish expressing RUNX1-ETO, MOZ/TIF2 transgenic zebrafish, gain-of-function mutant zebrafish of receptor tyrosine kinase FLT3, human NPMc+ transgenic zebrafish, transgenic zebrafish expressing murine Mycn gene and a variety of zebrafish acute myeloid leukemia models such as zebrafish carrying the hypomorphic spi1 mutant allele.

MOZ/TIF2 transgenic zebrafish, characterized by accumulation of immature myeloid cells in the renal bone marrow, but reduced numbers of lymphocytes and precursor cells in the spleen. Zebrafish gain-of-function mutants of the receptor tyrosine kinase FLT3 exhibit myeloid cell expansion similar to human AML. Human NPMc+ transgenic zebrafish characterized by increased spi1+ myeloid precursors followed by expansion of mpo+ and csf1r+ cells. Transgenic zebrafish expressing the murine Mycn gene are characterized by enhanced cell proliferation and accumulation of immature blasts, increased myelopoiesis, and anemia, with immature myeloblasts observed in peripheral blood, renal bone marrow, and spleen. Zebrafish harboring a mutant allele of the hypomorphic spi1 exhibit an overproduction of immature granulocytes in tail hematopoietic tissue at 3 dpf, which is very similar to some aspects of human myelodysplastic syndrome (MDS)/AML.

Finally, our zebrafish models can be used not only for forward genetic screens to identify novel genes associated with human hematological malignancies. They can also be used for high-throughput chemical inhibition screening to accelerate the development of acute myeloid leukemia therapies. If you would like to know anything about the zebrafish acute myeloid leukemia models, please feel free to contact us.

Advantages

• High-throughput gene and drug screening
• Rapidly perform reverse and forward genetic screening
• Observe different cells and tissues in real time
• Track labeled cancer cells in in vivo imaging analysis, enabling the study of metastatic processes as well as key tumor cell microenvironment growth properties such as angiogenesis

References

1. Rasighaemi P, et al. Zebrafish as a model for leukemia and other hematopoietic disorders. J Hematol Oncol. 2015, 8:29.
2. Molina B, et al. Zebrafish models of acute leukemias: Current models and future directions. Wiley Interdiscip Rev Dev Biol. 2021, 10(6):e400.

For research use only. Not intended for any clinical use.