| Project/Area Number |
15591081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
FUJII Kunihiro (2004) Tohoku University, Hospital, Research Associate, 病院, 助手 (20344674)
今泉 益栄 (2003) 東北大学, 大学院・医学系研究科, 助教授 (40191895)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAWARA Akira Tohoku University, Hospital, Lecturer, 病院・講師 (90270834)
TANAKA Takashi Tohoku University, Hospital, Research Associate, 病院・助手 (10292335)
藤井 邦裕 東北大学, 医学部附属病院, 助手 (20344674)
佐藤 篤 東北大学, 医学部附属病院, 助手 (20292336)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Acute promyelocytic leukemia / mutant PML-RARa / ATRA-resistance / Am80 / Am80 / PML / MRDモニタリング / FLT3遺伝子 / 急性前骨髄球性白血病 / 変異PML-RARα / 分子標的療法 / アポトーシス |
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| Research Abstract |
Study on ATRA-resistance caused by mutant PML-RAR α ; In this study, we examined the cellular and molecular RA-response of a human APL cell line, UF-1, established from a patient who had ATRA-resistance and a mutation in the PML-RAR α chimeric protein. For cellular RA-response, differentiation and apoptosis was evaluated in UF-1 cells treated with retinoids. For molecular RA-response, RA-dependent transcriptional activity of PML-RARa chimeric protein and RT-PCR of PML-RAR α, RAR α, RAR β, and RAR γ was determined. In response to ATRA and Am80 at 100 nM or lower doses, neither cellular nor molecular RA-response was detected. By contrast, in response to 1 □M ATRA and Am80, UF-1 showed a full-scaled maturation with apoptosis, whereas molecular RA-response of the mutant PML-RARa was insufficient. These findings suggest that the dose-dependently altered ATRA-response of UF-1 cells may be determined through the interaction between the mutant PML-RARa and other intrinsic nuclear RA receptors.
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