2006 Fiscal Year Final Research Report Summary
Comprehensive analysis of oncogenic transcriptional factor Evi-1.
| Project/Area Number |
17390273
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUROKAWA Mineo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (80312320)
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| Co-Investigator(Kenkyū-buntansha) |
HANGAISHI Akira The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 特任講師 (20344450)
IZUTSU Koji The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (30361471)
GOYAMA Susumu The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 医員 (80431849)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Evi-1 / leukemia / isoform / oligomerization / knockout mice / hematopoietic stem cell |
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| Research Abstract |
Evi-1 is a member of the SET/PR domain family of transcription factors whose inappropriate expression leads to leukemic transformation. Two distinct alternative forms, Evi-1a and Evi-1c, are generated from the Evi-1 gene. Although Evi-1a (PR-absent form) is widely recognized as an oncoprotein, a role for Evi-1c (PR-containing form) in leukemogenesis has not been elucidated. In this study, we showed that Evi-la forms homo-oligomers while Evi-1c exclusively exists as a monomer. Remarkably, Evi-1c has lost the ability to interact with CtBP, and to repress TGF-β signaling. These results indicate that oligomeraization contributes to the oncogenic potential of Evi-1.
Next, We created Evi-1 mutant mice to investigate the in vivo role of Evi-1 in hematopoiesis and leukemogenesis. Using these mice, we showed that Evi-1 regulates proliferative capacity of hematopoietic stem cells in a dose-dependent manner both during embryogenesis and in adults. In contrast, Evi-1 is dispensable for blood cell lineage commitment. We further demonstrated that disruption of Evi-1 in leukemic cells transformed by MLL/ENL or E2A/HLF leads to significant loss of their proliferative activity. These results suggest that Evi-1 is a critical regulator for the proliferation of normal and leukemic cells.
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Research Products
(12 results)
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[Journal Article] A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma : a single-institution study.2007
Author(s)
Nitta E, Izutsu K, Sato T, Ota Y, Takeuchi K, Kamijo A, Takahashi K, Oshima K, Kanda Y, Chiba S, Motokura T, Kurokawa M
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Journal Title
Annals of Oncology 18・2
Pages: 364-369
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation.2007
Author(s)
Kako S, Kanda Y, Sato T, Goyama S, Noda N, Shoda E, Oshima K, Inoue M, Izutsu K, Watanabe T, Motokura T, Chiba S, Fukayama M, Kurokawa M
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Journal Title
American Journal of Hematology 82・5
Pages: 386-390
Description
「研究成果報告書概要(和文)」より
-
[Journal Article] A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive β-cell lymphoma : a single-institution study.2007
Author(s)
Nitta E, Izutsu K, Sato T, Ota Y, Takeuchi K, Kamijo A, Takahashi K, Oshima K, Kanda Y, Chiba S, Motokura T, Kurokawa M.
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Journal Title
Annals of Oncology. 18(2)
Pages: 364-369
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation.2007
Author(s)
Kako S, Kanda Y, Sato T, Goyama S, Noda N, Shoda E, Oshima K, Inoue M, Izutsu K, Watanabe T, Motokura T, Chiba S, Fukayama M, Kurokawa M.
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Journal Title
American Journal of Hematology. 82(5)
Pages: 386-390
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] FDG-PET in T-cell and NK-cell neoplasms.
Author(s)
Kako S, Izutsu K, Ohta Y, Minatani Y, Sugaya M, Momose T, Ohtomo K, Kanda Y, Chiba S, Motokura T, Kurokawa M
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Journal Title
Annals of Oncology (in press)
Description
「研究成果報告書概要(和文)」より
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[Journal Article] FDG-PET in T-cell and NK-cell neoplasms.
Author(s)
Kako S, Izutsu K, Ohta Y, Minatani Y, Sugaya M, Momose T, Ohtomo K, Kanda Y, Chiba S, Motokura T, Kurokawa M.
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Journal Title
Annals of Oncology (in press)
Description
「研究成果報告書概要(欧文)」より
