title: New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins.
abstract: BACKGROUND
  Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins.
  
  
  OBJECTIVE
  In this review, we aim to summarize these new developments while also providing a historic overview of the related early studies.
  
  
  METHODS
  A total of 218 publications were reviewed in this article, a majority of which were published after 2004.We also downloaded 3D structures of AML1-ETO domains from Protein Data Bank and provided a systematic summary of their structures.
  
  
  RESULTS
  By reviewing the literature, we summarized early and recent findings on AML1-ETO, including its protein-protein interactions, transcriptional and leukemogenic mechanisms, as well as the recently reported involvement of ETO family corepressors in regulating the function of E2A-Pbx1.
  
  
  CONCLUSIONS
  While the recent development in genomic and structural studies has clearly demonstrated that the fusion proteins function by directly regulating transcription, a further understanding of the underlying mechanisms, including crosstalk with other transcription factors and cofactors, and the protein-protein interactions in the context of native proteins, may be necessary for the development of highly targeted drugs for leukemia therapy.
authors.affiliation: Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Steinauer
authors.affiliation: Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhang
keywords: AML1-ETO; E-proteins; E2A-Pbx1; chromosomal translocation; leukemia; transcription