| Project/Area Number |
04253208
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | University of Tokyo |
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Principal Investigator |
HIRAI Hisamaru University of Tokyo, 3rd Dept.of Internal Med., Lecturer, 医学部(病), 講師 (90181130)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Seishi University of Tokyo, 3rd Dept.of Internal Med., Medical Fellow, 医学部(病), 医員
MITANI Kinuko University of Tokyo, 3rd Dept.of Internal Med., Assistant Pro., 医学部(病), 助手 (50251244)
杉本 耕一 東京大学, 医学部(病), 医員
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥19,000,000 (Direct Cost: ¥19,000,000)
Fiscal Year 1993: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1992: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | t(3 ; 21) translocation / chronic myelocytic leukemia / blastic crisis / AML1 / EVI-1 chimeric gene / AML1 gene / EVI-1 gene / transcription factor / N-ras遺伝子 / p53遺伝子 / Ph^1陽性ALL / CML急性転化 / 骨髄異形成症候群 / 白血病 / SSCP法 / PCR法 |
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| Research Abstract |
The t(3 ; 21)(q26 ; q22) translocation is thought to trigger blastic crisis in chronic myelocytic leukemia (CML). This reciprocal translocation generates an AML1/EVI-1 chimeric gene which is transcribed as fusion mRNAs. The 180 kD AML1/EVI-1 fusion protein contains an amino-terminal half of AML1 including a runt homology domain which is fused to the entire of zinc finger EVI-1 protein. The AML1/EVI-1 fusion transcript is consistent among all three cases of the t(3 ; 21)-carrying leukemia examined. Synthetic antisense oligonucleotides complementary to the sequences including the transcriptional initiation sequences of authentic AML1 and EVI-1 specifically suppress growth of leukemia cells with the t(3 ; 21) translocation. These findings strongly suggest that the t(3 ; 21) translocation results in the formation of a new class of a chimeric transcription factor which could contribute to leukemic progression through interference with cell growth and differentiation.
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