Zebrafish B cell acute lymphoblastic leukemia: new findings in an old model

Abstract

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 (<i>Danio rerio</i>) T-ALL models have been reported, but until recently, robust <i>D. rerio</i> B-ALL models were not described. Then, <i>D. rerio</i> 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 <i>MYC</i> (<i>hMYC</i>). We describe B-ALL incidence in a large cohort of <i>hMYC</i> 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 <i>D. rerio</i> 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.