Zebrafish blastomere screen identifies retinoic acid suppression of MYB in adenoid cystic carcinoma

J Exp Med. 2018 Oct 1;215(10):2673-2685. doi: 10.1084/jem.20180939. Epub 2018 Sep 12.


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 MYB-driven tumors, we developed a pluripotent zebrafish blastomere culture system. We performed a chemical genetic screen and identified retinoic acid agonists as suppressors of c-myb expression. Retinoic acid treatment also decreased c-myb gene expression in human leukemia cells. Translocations that drive overexpression of the oncogenic transcription factor MYB 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastomeres / immunology*
  • Blastomeres / pathology
  • Carcinoma, Adenoid Cystic / drug therapy*
  • Carcinoma, Adenoid Cystic / genetics
  • Carcinoma, Adenoid Cystic / immunology
  • Carcinoma, Adenoid Cystic / pathology
  • Humans
  • Mice
  • Mice, Nude
  • Proto-Oncogene Proteins c-myb / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-myb / genetics
  • Proto-Oncogene Proteins c-myb / immunology
  • Salivary Gland Neoplasms / drug therapy*
  • Salivary Gland Neoplasms / genetics
  • Salivary Gland Neoplasms / immunology
  • Salivary Gland Neoplasms / pathology
  • Tretinoin / pharmacology*
  • U937 Cells
  • Xenograft Model Antitumor Assays
  • Zebrafish / genetics
  • Zebrafish / immunology*
  • Zebrafish Proteins / antagonists & inhibitors*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / immunology


  • Proto-Oncogene Proteins c-myb
  • Zebrafish Proteins
  • Tretinoin