ZFIN ID: ZDB-PUB-180914-4
Zebrafish blastomere screen identifies retinoic acid suppression of MYB in adenoid cystic carcinoma.
Mandelbaum, J., Shestopalov, I.A., Henderson, R.E., Chau, N.G., Knoechel, B., Wick, M.J., Zon, L.I.
Date: 2018
Source: The Journal of experimental medicine   215(10): 2673-2685 (Journal)
Registered Authors: Shestopalov, Ilya, Zon, Leonard I.
Keywords: none
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
PubMed: 30209067 Full text @ J. Exp. Med.
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.