ZFIN ID: ZDB-PUB-090204-22
Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation
Yeh, J.R., Munson, K.M., Elagib, K.E., Goldfarb, A.N., Sweetser, D.A., and Peterson, R.T.
Date: 2009
Source: Nature Chemical Biology   5(4): 236-243 (Journal)
Registered Authors: Peterson, Randall, Yeh, Jing-Ruey (Joanna)
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Dinoprostone
  • Gene Expression Regulation/drug effects
  • Gene Expression Regulation/physiology
  • Humans
  • K562 Cells
  • Nitrobenzenes
  • Oncogene Proteins/genetics
  • Oncogene Proteins/metabolism*
  • Small Molecule Libraries
  • Sulfonamides
  • Transcription Factors
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
  • beta Catenin
PubMed: 19172146 Full text @ Nat. Chem. Biol.
It has been proposed that inhibitors of an oncogene's effects on multipotent hematopoietic progenitor cell differentiation may change the properties of the leukemic stem cells and complement the clinical use of cytotoxic drugs. Using zebrafish, we developed a robust in vivo hematopoietic differentiation assay that reflects the activity of the oncogene AML1-ETO. Screening for modifiers of AML1-ETO-mediated hematopoietic dysregulation uncovered unexpected roles of COX-2- and beta-catenin-dependent pathways in AML1-ETO function. This approach may open doors for developing therapeutics targeting oncogene function within leukemic stem cells.