Review

Frontiers of Medicine

, Volume 6, Issue 3, pp 248-262

AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

  • Megan A. HatlenAffiliated withMolecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer CenterWeill Cornell Medical College
  • , Lan WangAffiliated withMolecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center
  • , Stephen D. NimerAffiliated withMolecular Pharmacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer CenterWeill Cornell Medical College Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.

Keywords

AML1-ETO mouse model leukemia t(8;21) pathway hits mutation hematopoiesis Kasumi-1 CD34+