Zebrafish B cell acute lymphoblastic leukemia: new findings in an old model
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Gilseung Park1,*, Jessica Burroughs-Garcia2,*, Clay A. Foster3,*, Ameera Hasan4, Chiara Borga2 and J. Kimble Frazer1,2,4
1 Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2 Department of Pediatrics, Section of Pediatric Hematology-Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
3 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA
4 Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
* These authors contributed equally to this work
|J. Kimble Frazer,||email:||Kimble-Frazer@ouhsc.edu|
Keywords: acute lymphoblastic leukemia; ALL; zebrafish; lymphocyte; MYC
Received: November 13, 2019 Accepted: March 19, 2020 Published: April 14, 2020
Acute lymphoblastic leukemia (ALL) is the most common pediatric, and ninth most common adult, cancer. ALL can develop in either B or T lymphocytes, but B-lineage ALL (B-ALL) exceeds T-ALL clinically. As for other cancers, animal models allow study of the molecular mechanisms driving ALL. Several zebrafish (Danio rerio) T-ALL models have been reported, but until recently, robust D. rerio B-ALL models were not described. Then, D. rerio B-ALL was discovered in two related zebrafish transgenic lines; both were already known to develop T-ALL. Here, we report new B-ALL findings in one of these models, fish expressing transgenic human MYC (hMYC). We describe B-ALL incidence in a large cohort of hMYC fish, and show B-ALL in two new lines where T-ALL does not interfere with B-ALL detection. We also demonstrate B-ALL responses to steroid and radiation treatments, which effect ALL remissions, but are usually followed by prompt relapses. Finally, we report gene expression in zebrafish B lymphocytes and B-ALL, in both bulk samples and single B- and T-ALL cells. Using these gene expression profiles, we compare differences between the two new D. rerio B-ALL models, which are both driven by transgenic mammalian MYC oncoproteins. Collectively, these new data expand the utility of this new vertebrate B-ALL model.
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