title: The shortest isoform of C/EBPβ, liver inhibitory protein (LIP), collaborates with Evi1 to induce AML in a mouse BMT model.
abstract: Ecotropic viral integration site 1 (Evi1) is one of the master regulators in the development of acute myeloid leukemia (AML) and myelodysplastic syndrome. High expression of Evi1 is found in 10% of patients with AML and indicates a poor outcome. Several recent studies have indicated that Evi1 requires collaborative factors to induce AML. Therefore, the search for candidate factors that collaborate with Evi1 in leukemogenesis is one of the key issues in uncovering the mechanism of Evi1-related leukemia. Previously, we succeeded in making a mouse model of Evi1-related leukemia using a bone marrow transplantation (BMT) system. In the Evi1-induced leukemic cells, we identified frequent retroviral integrations near the CCAAT/enhancer-binding protein β (C/EBPβ) gene and overexpression of its protein. These findings imply that C/EBPβ is a candidate gene that collaborates with Evi1 in leukemogenesis. Cotransduction of Evi1 and the shortest isoform of C/EBPβ, liver inhibitory protein (LIP), induced AML with short latencies in a mouse BMT model. Overexpression of LIP alone also induced AML with longer latencies. However, excision of all 3 isoforms of C/EBPβ (LAP*/LAP/LIP) did not inhibit the development of Evi1-induced leukemia. Therefore, isoform-specific intervention that targets LIP is required when we consider C/EBPβ as a therapeutic target.
authors.affiliation: Department of Hematology & Oncology, Graduate School of Medicine, Universityof Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe-Okochi
authors.forename: Akihide
authors.initials: A
authors.lastname: Yoshimi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Sato
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.forename: Kazuki
authors.initials: K
authors.lastname: Taoka
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Satoh
authors.forename: Akihito
authors.initials: A
authors.lastname: Shinohara
authors.forename: Takako
authors.initials: T
authors.lastname: Tsuruta
authors.forename: Akiko
authors.initials: A
authors.lastname: Masuda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yokota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Koki
authors.initials: K
authors.lastname: Takahashi
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000473:pathology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011519:Proto-Oncogenes / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D020033:Protein Isoforms; D014157:Transcription Factors