Project/Area Number |
08557018
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Human pathology
|
Research Institution | The University of Tokyo |
Principal Investigator |
MORI Shigeo The University of Tokyo, The Institiute of Medical Science, Professor, 医科学研究所, 教授 (30010424)
|
Co-Investigator(Kenkyū-buntansha) |
WATANABE Toshiki The University of Tokyo, The Institiute of Medical Science, Associate Professor, 医科学研究所, 助教授 (30182934)
YAMAMOTO Tadashi The University of Tokyo, The Institiute of Medical Science, Professor, 医科学研究所, 教授 (40134621)
|
Project Period (FY) |
1996 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥15,500,000 (Direct Cost: ¥15,500,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1996: ¥7,500,000 (Direct Cost: ¥7,500,000)
|
Keywords | malignant lymphoma / BCL6 gene / chromosomal translocation / mRNA / chimeric protein / リンパ腫 / 染色体 / p80NPM / ALK / キメラ蛋白質 / 未分化大細胞型リンパ腫 / ALK遺伝子 / TLS / CHOP遺伝子 / bcl6遺伝子 |
Research Abstract |
The chimeric gene is a unique non-natural gene made by the fusion of two different genes, causing production of a novel protein with the head and tail parts made of two different genes. Some of such chimeric protein cause specific diseases like soft part sarcoma and malignant lymphomas. This study was aimed (1)to identify new pathogenetic chimeric genes/proteins, (2)Biological function of chimeric proteins, (3)Application of chimeric proteins in the diagnosis and treatment of human diseases. (1) Identification of new pathogenetic chimeric genes/proteins : Over 20 chimeric genes were identified from human malignant lymphomas a part of which was derived from BCL6 gene. Some of them were found to be new genes. Also, a new type of TLS/FUS-CHOP chimeric gene was identified from human liposarcoma tissues. (2) Biological function of chimeric proteins : A part of the biological functions of NPM/ALK chimeric protein was clarified. Also, the biological function of BCL6 gene product was partly clarified. (3) Application of chimeric proteins in the diagnosis and treatment of human diseases : With the introduction of newly developed antibody to NPM/ALK chimeric protein, we invested an easy and conclusive diagnostic method for the NPM/ALK chimera-related human diseases. Also, we could transfer over 20 cases of human malignant lymphomas bearing different types of chimera genes. This cell line is now under study for the targeting of these genes in immunotherapy.
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