1996 Fiscal Year Final Research Report Summary
Molecular Analysis of Maturation Arrest Mechanism of Myeloid Leukemogenesis
| Project/Area Number |
06404039
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 |
ASANO Shigetaka Univ of Tokyo, Inst of Med Sci, Professor, 医科学研究科, 教授 (50134614)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Satoshi Univ of Tokyo, IInst of Med Sci, Research Associate, 医科学研究所, 助手 (60226834)
MORISHITA Kazuhiro National Inst of Cancer Research, Section Head, 室長 (80260321)
TOJO Arinobu Univ of Tokyo, IInst of Med Sci, Assistant Professor, 医科学研究科, 講師 (00211681)
TANI Kenzaburo Univ of Tokyo, IInst of Med Sci, Associated Professor, 医科学研究科, 助教授 (00183864)
SATO Noriharu Univ of Tokyo, IInst of Med Sci, Associated Professor, 医科学研究科, 助教授 (90162461)
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| Project Period (FY) |
1994 – 1996
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| Keywords | transcriptional factor / maturation arrest / GIG-1 / neutrophil / NK cell / PEBP2 alpha / PEBP2 beta / Evi-1 |
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| Research Abstract |
We have been focusing on the molecular analysis of maturation arrest mechanism underlying the myeloid leukemogenesis using myeloid marker genes, cell cycle related genes and trancriptional factor genes. First of all, we have cloned a novel myeloid cell marker gene of GIG-1 (G-CSF inducible gene-1) from G-CSF stimulated leukemia cells from CML patients. The results demonstrated that GIG-1gene was expressed in myeloid lineage cells at the levels of mRNA and protein. This novel gene was paricularly expressed more in matured cells at protein levels. The elecromicroscopic results revealed the microsomal localization of this protein. The expression of this novel gene together with other myeloid specific marker genes of alkaline phosphatase, myeloperoxidase, defensin are very important to analyze the molecular mechanisms of maturation arrest. Second, we tried to analyze the first event which induced the maturation arrest of myeloid cell lineage. Particulary we focused on PEBP2 alpha and PEBP2 beta genes, DNA binding and DNA nonbinding transcriptional regulating genes respectively, forming heterodimers and both of them are considered strongly involoved in leukemogenesis. The embryos of knockout mice of the PEBP2 beta revealed the severe pictures of hematopoiesis including maturation arrest of the myeloid cells. As the defect of PEBP2 a gene was also reported to be strongly involved in the suppressed hematopoiesis in knockout mice, both of these molecules are consiered to be one of the responsible molecule of maturation arrest found in myeloid leukemia. The use of the normal counterpart genes might be useful for some types of myeloid leukemia with the genetic disruptios of PEBP2 alpha or PEBP2 beta. We also studied the roles of othere transcriptional factors including Evi-1 and cell cycle specific molecules for elucidating the roles of these molecules in the maturation arrest of myeloid leukemia cells.
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