Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

Borga, C.; Park, G.; Foster, C.; Burroughs-Garcia, J.; Marchesin, M.; Ahmed, S. T.; Bresolin, S.; Batchelor, L.; Scordino, T.; Miles, R. R.; te Kronnie, G.; Regens, J. L.; Frazer, J. K.

doi:10.1101/281469

bioRxiv · 10.1101/281469

Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis

Borga, C.·Park, G.·Foster, C.·Burroughs-Garcia, J.·Marchesin, M.·Ahmed, S. T.·Bresolin, S.·Batchelor, L.·Scordino, T.·Miles, R. R.·te Kronnie, G.·Regens, J. L.·Frazer, J. K.

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Abstract

Precursor-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer, but there are no useful zebrafish pre-B ALL models. We describe the first highly-penetrant zebrafish pre-B ALL, driven by human MYC. Leukemias express B lymphoblast-specific genes and are distinct from T cell ALL (T-ALL)--which these fish also develop. Zebrafish pre-B ALL shares in vivo features and expression profiles with human pre-B ALL, and these profiles differ from zebrafish T-ALL or normal B and T cells. These animals also exhibit aberrant lymphocyte development. As the only robust zebrafish pre-B ALL model and only example where T-ALL also develops, this model can reveal differences between MYC-driven pre-B vs. T-ALL and be exploited to discover novel pre-B ALL therapies.\n\nStatement of significanceWe describe the first robust zebrafish pre-B ALL model in MYC-transgenic animals known to develop T-ALL, revealing the only animal model with both human ALL types. We also describe aberrant multi-lineage lymphopoiesis. This powerful system can be used to study MYC-driven leukemogenesis and discover new pre-B ALL targeted therapies.

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Borga, C., Park, G., Foster, C., Burroughs-Garcia, J., Marchesin, M., Ahmed, S. T., Bresolin, S., Batchelor, L., Scordino, T., Miles, R. R., te Kronnie, G., Regens, J. L., Frazer, J. K.. 2018-03-13. Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by transgenic MYC: implications for oncogenesis and lymphopoiesis. https://doi.org/10.1101/281469

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