Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation.
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.
Yeh
Jing-Ruey J
JR
Developmental Biology Laboratory, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Munson
Kathleen M
KM
Elagib
Kamaleldin E
KE
Goldfarb
Adam N
AN
Sweetser
David A
DA
Peterson
Randall T
RT
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D015232:Dinoprostone; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020014:K562 Cells; D009578:Nitrobenzenes; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D054852:Small Molecule Libraries; D013449:Sulfonamides; D014157:Transcription Factors; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*; D051176:beta Catenin
D009578:Nitrobenzenes; D015513:Oncogene Proteins; D054852:Small Molecule Libraries; D013449:Sulfonamides; D014157:Transcription Factors; D029961:Zebrafish Proteins; D051176:beta Catenin; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D015232:Dinoprostone