PUBLICATION
Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation
- Authors
- Yeh, J.R., Munson, K.M., Elagib, K.E., Goldfarb, A.N., Sweetser, D.A., and Peterson, R.T.
- ID
- ZDB-PUB-090204-22
- 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.
Citation
Yeh, J.R., Munson, K.M., Elagib, K.E., Goldfarb, A.N., Sweetser, D.A., and Peterson, R.T. (2009) Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation. Nature Chemical Biology. 5(4):236-243.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping