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Nat Chem Biol. 2009 Apr;5(4):236-43. doi: 10.1038/nchembio.147. Epub 2009 Jan 26.

Discovering chemical modifiers of oncogene-regulated hematopoietic differentiation.

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  • 1Developmental Biology Laboratory, Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.

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.

PMID:
19172146
[PubMed - indexed for MEDLINE]
PMCID:
PMC2658727
Free PMC Article

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