title: Oncogenic pathways of AML1-ETO in acute myeloid leukemia: multifaceted manipulation of marrow maturation.
abstract: The leukemic fusion protein AML1-ETO occurs frequently in human acute myeloid leukemia (AML) and has received much attention over the past decade. An initial model for its pathogenetic effects emphasized the conversion of a hematopoietic transcriptional activator, RUNX1 (or AML1), into a leukemogenic repressor which blocked myeloid differentiation at the level of target gene regulation. This view has been absorbed into a larger picture of AML1-ETO pathogenesis, encompassing dysregulation of hematopoietic stem cell homeostasis at several mechanistic levels. Recent reports have highlighted a multifaceted capacity of AML1-ETO directly to inhibit key hematopoietic transcription factors that function as tumor suppressors at several nodal points during hematopoietic differentiation. A new model is presented in which AML1-ETO coordinates expansion of the stem cell compartment with diminished lineage commitment and with genome instability.
authors.affiliation: Department of Pathology, University of Virginia School of Medicine, P.O. Box 800904, Charlottesville, VA 22908, USA.
authors.forename: Kamaleldin E
authors.initials: KE
authors.lastname: Elagib
authors.forename: Adam N
authors.initials: AN
authors.lastname: Goldfarb
mesh_terms: D000208:Acute Disease; D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D002454:Cell Differentiation; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D025521:Tumor Suppressor Proteins / Q000187:drug effects
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D025521:Tumor Suppressor Proteins