title: AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1.
abstract: AML1-ETO, a chimeric gene frequently detected in acute myelogenous leukemia (AML), inhibits the differentiation of myeloid progenitors by suppressing genes associated with myeloid differentiation and increases the replating ability of clonogenic myeloid progenitors. However, AML1-ETO alone cannot induce AML and thus additional genetic events are required for the onset of AML. The Wilms tumor gene (WT1), which has been identified as the gene responsible for Wilms tumor, is expressed at high levels in almost all human leukemias. In this study, we have generated transgenic mice (WT1-Tg) that overexpress WT1 in hematopoietic cells to investigate the effects of WT1 on AML1-ETO-associated leukemogenesis. AML1-ETO-transduced bone marrow (BM) cells from WT1-Tg mice exhibited inhibition of myeloid differentiation at more immature stages and higher in vitro colony-forming ability compared with AML1-ETO-transduced BM cells from wild-type mice. Most importantly, all of the mice that received a transplant of AML1-ETO-transduced BM cells from the WT1-Tg mice rapidly developed AML. These results demonstrate that AML1-ETO may exert its leukemogenic function in cooperation with the expression of WT1.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, 1-7, Yamada-Oka, Suita City, Osaka 565-0871, Japan.
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kanato
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagihara
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nakatsuka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshida
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Yukie
authors.initials: Y
authors.lastname: Harada
authors.forename: Naoya
authors.initials: N
authors.lastname: Tatsumi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Aozasa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D023461:Myeloid Progenitor Cells / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein; D014161:Transduction, Genetic; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
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; D025721:WT1 Proteins