Mandelbaum J, Shestopalov IA, Henderson RE, Chau NG, Knoechel B, Wick MJ, Zon LI. 2018. Zebrafish blastomere screen identifies retinoic acid suppression of in adenoid cystic carcinoma. The Journal of experimental medicine. 215(10):2673-2685. Pubmed: 30209067 DOI:10.1084/jem.20180939


Pluripotent cells have been used to probe developmental pathways that are involved in genetic diseases and oncogenic events. To find new therapies that would target -driven tumors, we developed a pluripotent zebrafish blastomere culture system. We performed a chemical genetic screen and identified retinoic acid agonists as suppressors of expression. Retinoic acid treatment also decreased gene expression in human leukemia cells. Translocations that drive overexpression of the oncogenic transcription factor are molecular hallmarks of adenoid cystic carcinoma (ACC), a malignant salivary gland tumor with no effective therapy. Retinoic acid agonists inhibited tumor growth in vivo in ACC patient-derived xenograft models and decreased MYB binding at translocated enhancers, thereby potentially diminishing the MYB positive feedback loop driving ACC. Our findings establish the zebrafish pluripotent cell culture system as a method to identify modulators of tumor formation, particularly establishing retinoic acid as a potential new effective therapy for ACC.
© 2018 Mandelbaum et al.

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Photo of Len Zon

The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.

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