title: AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches.
abstract: The AML1-ETO fusion transcription factor is generated by the t(8;21) translocation, which is present in approximately 4%-12% of adult and 12%-30% of pediatric acute myeloid leukemia (AML) patients. Both human and mouse models of AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the absence of secondary events. In this review, we discuss the pathogenetic insights that have been gained from identifying the various events that can cooperate with AML1-ETO to induce AML in vivo. We also discuss potential therapeutic strategies for t(8;21) positive AML that involve targeting the fusion protein itself, the proteins that bind to it, or the genes that it regulates. Recently published studies suggest that a targeted therapy for t(8;21) positive AML is feasible and may be coming sometime soon.
authors.affiliation: Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Megan A
authors.initials: MA
authors.lastname: Hatlen
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C107844:AML1-ETO fusion protein, human; D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; C493726:Runx1 protein, mouse; D014157:Transcription Factors