| Project/Area Number |
16390272
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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 |
OGAWA Seishi The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 寄附講座教員 (60292900)
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| Co-Investigator(Kenkyū-buntansha) |
CHIBA Shigeru The University of Tokyo, Faculty of Medicine, Assistant Professor, 医学部附属病院, 助教授 (60212049)
SUZUKI Takahiro The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 寄附講座教員 (40345210)
KUMANO Keiki The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 研究拠点形成特任研究員 (90396721)
IZUTSU Koji The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (30361471)
YAMAMOTO Go The University of Tokyo, Faculty of Medicine, Medical Staff, 医学部附属病院, 医員 (70396753)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | Leukemia / Copy number analysis / SNP array / CNAG / Allele-specific analysis / UPD / LOH / マイクロアレイ / Blimp1 / 細胞周期 / モデルマウス / Affymetrix |
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| Research Abstract |
Leukemia is a neoplastic state in which deregulated cell division, differentiaion, and apoptosis lead to unregulated clonal proliferation of hematopoietic progenitors and the molecular basis for these abnormalities should be finally ascribed to the genetic alterations in leukemia genome. Thus the identification of those genetic changes is of crucial importance for the understanding of leukemogeneic mechanism. The purpose of this study is exploring leukemia genomes for genetic abnormalities using advanced microarray technologies, identifying their molecular targets and clarifying the leukemogenic mechanism through analysis of the target molecules using mouse genetics. In this study, we newly developed a robust system for copy number detection of cancer genome using high-density oligonucleotide microarrays (CNAG) and comprehensively analyzed copy number alterations in leukemia genomes. We analyzed a total of 886 leukemia samples and found numerous copy number abnormalities, including those that are commonly involved in multiple samples. Due to the extremely high resolution, the candidate gene that might be relevant to leukemogenesis was uniquely identified for many abnormal regions. Blimp1 is one of such target found in a homozygous deletion at 6q21 in ATL. Interestingly, conditional Blimp1 targeted mice show lymphonode swelling as well as splenomegaly. In addition, we revealed that it is mutated in primary ATL samples and when expressed in Hela cells, induces cell arrest at both G1 and G2 phases, indicating its tumor suppressive function.
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