2003 Fiscal Year Final Research Report Summary
Analysis of tumor supressor genes p16 and Rb in childhood acute lymphoblastic leukemia
| Project/Area Number |
14570734
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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 | University of Yamanashi (2003)
山梨医科大学 (2002) |
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Principal Investigator |
SUGITA Kanji University of Yamanashi, Hospital, Assistant professor, 医学部附属病院, 講師 (60138055)
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| Co-Investigator(Kenkyū-buntansha) |
GOI Kumiko University of Yamanashi, Hospital, Research Associate, 医学部附属病院, 助手 (70324192)
INUKAI Takeshi University of Yamanashi, Interdisciplinary Graduate School of medicine and Engineering, Research Associate, 大学院・医学工学総合研究部, 助手 (30293450)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Rb gene / p16 gene / Cell cycle / ALL |
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| Research Abstract |
Progression of the cell cycle is cooperatively regulated by a series of cyclin and cyclin-dependent kinase (CDK) complexes which elicit phosphorylation of retinoblastoma protein (Rb) resulting in release of several RB-associated transcription factors such as the E2F family required for G1 to S phase progression. p16/INK4a negatively regulates this process as one of CDK inhibitors, and is regarded as a tumor suppressor because of its frequent inactivation in a wide variety of tumors. Unexpectedly, however, recent reports have revealed the association of an enhanced p16 expression with an unfavorable outcome in several malignancies including childhood ALL. Along with the process of our study characterizing p16 in childhood ALL, we found a B-precursor ALL cell line (KOPN-79) with nonrandom translocations expressing p16 at extremely high levels. To clarify mechanism(s) allowing this cell line to cell cycle progression, we examined key regulators in the p16/Rb pathway, and identify the structural abnormality of the Rb gene. The resultant Rb product was rearranged and truncated at the site within the pocket region, and showed the poor binding capacity to the E2F-1. Our findings might explain, at least in part, the primary cause for an unfavorable outcome of childhood ALL over-expressing p16.
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Research Products
(12 results)
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[Publications] Kobayashi N, Agematsu K, Sugita K, Sako M, Nonoyama S, Yachie A, Kumaki S, Kumaki S, Tsuchiya S, Ochs HD, Sugita K, Fukushima Y, Komiyama A.: "Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families."Hum.Genet. 112. 348-352 (2003)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Uno K, Inukai T, Kayagaki N, Goi K, Sato H, Nemoto A, Takahashi K, Kagami K, Yamaguchi N, Yagita H, Okumura K, Koyama-Okazaki T, Suzuki T, Sugita K, Nakazawa S.: "TNF-related apoptosis-inducing ligand (TRAIL) frequently induces apoptosis in Philadelphia chromosome-positive leukemia cells."Blood. 101. 3658-3667 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Tsutsumi S, Taketani T, Nishimura K, Ge X, Taki T, Sugita K, Ishii E, Hanada R, Ohki M, Aburatani H, Hayashi Y.: "Two distinct gene expression signatures in pediatric acute lymphoblastic leukemia with MLL rearraements."Cancer Res. 15. 4882-4887 (2003)
Description
「研究成果報告書概要(欧文)」より
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