| Project/Area Number |
07042002
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Special Cancer Research |
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| Research Institution | University of Tokyo |
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Principal Investigator |
HIRAI Hisamaru Faculty of Med., University of Tokyo・lecturer, 医学部(病), 講師 (90181130)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Naoto Faculty of Med., University of Tokyo・research associate, 医学部(病), 医員
WITTE Owen UCLA, 医学部, 教授
UENO Hiroo Faculty of Med., University of Tokyo・research associate, 医学部(病), 医員
KUROKAWA Mineo Faculty of Med., University of Tokyo・research associate, 医学部(病), 医員
OGAWA Seishi Faculty of Med., University of Tokyo・research associate, 医学部(病), 医員
TANAKA Tomoyuki Faculty of Med., University of Tokyo・assistant professor, 医学部(病), 助手 (50227154)
HANAZONO Yutaka Faculty of Med., University of Tokyo・assistant professor, 医学部(病), 助手 (70251246)
MITANI Kinuko Faculty of Med., University of Tokyo・assistant professor, 医学部(病), 助手 (50251244)
QWEN Witte UCLA・professor
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| Project Period (FY) |
1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1995: ¥5,700,000 (Direct Cost: ¥5,700,000)
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| Keywords | Chronic Myelocytic Leukemia / Blastic Crisis / Evi-1 Gene / Cell Cycle / p16INK4A Gene / p53 Gene / RB Protein / Tumor Suppressor Gene |
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| Research Abstract |
Evi-1 is a transforming gene originally identified in a common integration site of murine leukemia retrovirus and mapped in human chromosome 3q26. It is overexpressed in retrovirus induced murine myeloid leukemias as well as human myeloid leukemias with 3q26 abnormalities, and thus thought to be responsible for both human and murine leukemogenesis. In this study, a possible involvement of the Evi-1 gene in blastic transformation of chronic myelocytic leukemia (CML) was examined by northern blot analysis, and the frequencies of its expression were compared between Japanese patients and American ones. Expression of the Evi-1 gene was detected in 48% of Japanese patients and 40% of American ones. Our results suggest that increased expression of the Evi-1 gene may play an important role in development of human leukemias, especially in progression from chronic phase to blastic crisis of CML even without 3q26 abnormalities.
It is now evident that the cell cycle machinery has a variety of elem
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ents negatively regulating cell cycle progression. Among these negative regulators in cell cycle control, however, only 4 have been shown to be consistently involved in development of human cancers as tumor suppressors : Rb (Retinoblastoma susceptibility protein), p53, and recently identified two cyclin-dependent kinase inhibitors, p16INK4A/MTS1 and p15INK4B/MTS2. Because there are functional interrelations among these negative regulators in the cell cycle machinery, it is particularly interesting to investigate the multiplicity of inactivations of these tumor suppressors in blastic transformation of CML.In order to address this point, we examined inactivations of these four genes in patients with blastic crisis of CML by Southern blot and PCR-SSCP analyzes. We also analyzed Rb protein expression by western blot analysis. The p16INK4A was homozygously deleted in 9% and 15% in Japanese patients and American ones. The p53 gene was mutated in 27% and 20%, and the RB protein was inactivated in 18% and 14% in Japanese patients and American ones, respectively. These results suggest that there are no significant differences in inactivation frequences of these tumor suppressors in blastic transformation of CML. Less
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