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Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression
http://hdl.handle.net/10458/0002000435
http://hdl.handle.net/10458/0002000435b3064b7f-cca1-4eec-b230-3425c3bc7141
| 名前 / ファイル | ライセンス | アクション |
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article (3.9 MB)
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| アイテムタイプ | 学術雑誌論文 / Journal Article(1) | |||||||||||||||
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| 公開日 | 2024-01-16 | |||||||||||||||
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| タイトル | Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression | |||||||||||||||
| 言語 | en | |||||||||||||||
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| 言語 | eng | |||||||||||||||
| キーワード | ||||||||||||||||
| 言語 | en | |||||||||||||||
| キーワード | GPR56 Expression | |||||||||||||||
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| 言語 | en | |||||||||||||||
| キーワード | Ecotropic Viral Integration Site (EVI1) | |||||||||||||||
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| 言語 | en | |||||||||||||||
| キーワード | Pyrrole-imidazole Polyamides (PIP) | |||||||||||||||
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| 言語 | en | |||||||||||||||
| キーワード | G Protein-coupled Receptors (GPR56) | |||||||||||||||
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| 言語 | en | |||||||||||||||
| キーワード | High EVI1 | |||||||||||||||
| 資源タイプ | ||||||||||||||||
| 資源タイプ | journal article | |||||||||||||||
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| アクセス権 | open access | |||||||||||||||
| 著者 |
サハ, ハシ ラニ
× サハ, ハシ ラニ× Kaneda-Nakashima, Kazuko× 下崎, 俊介× Suekane, Akira× サルカル, ビードン チャンドラ× Saito, Yusuke× 小河, 穂波× Nakahata, Shingo× 井上, 健太郎
WEKO
30742
× Watanabe, Takayoshi
× Nagase, Hiroki
× 森下, 和広 |
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| 内容記述タイプ | Abstract | |||||||||||||||
| 内容記述 | G protein-coupled receptor 56 (GPR56) is highly expressed in acute myeloid leukemia (AML) cells with high EVI1 expression (EVI1high AML). Because GPR56 is a transcriptional target of EVI1 and silencing of GPR56 expression induces apoptosis, we developed a novel drug to suppress GPR56 expression in EVI1high AML cells. For this purpose, we generated pyrrole-imidazole (PI) polyamides specific to GPR56 (PIP/56-1 or PIP/56-2) as nuclease-resistant novel compounds that interfere with the binding of EVI1 to the GPR56 promoter in a sequence-specific manner. Treatment of EVI1high AML cell lines (UCSD/AML1 and Kasumi-3) with PIP/56-1 or PIP/56-2 effectively suppressed GPR56 expression by inhibiting binding of EVI1 to its promoter, leading to suppression of cell growth with increased rates of apoptosis. Moreover, intravenous administration of PIP/56-1 into immunodeficient Balb/c-RJ mice subcutaneously transplanted with UCSD/AML1 cells significantly inhibited tumor growth and extended survival. Furthermore, organ infiltration by leukemia cells in immunodeficient Balb/c-RJ mice, which were intravenously transplanted using UCSD/AML1 cells, was successfully inhibited by PIP/56-1 treatment with no apparent effects on murine hematopoietic cells. In addition, PIP treatment did not inhibit colony formation of human CD34+ progenitor cells. Thus, PI polyamide targeting of GPR56 using our compound is promising, useful, and safe for the treatment of EVI1high AML. | |||||||||||||||
| 言語 | en | |||||||||||||||
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| 内容記述タイプ | Other | |||||||||||||||
| 内容記述 | citeation: Saha HR, Kaneda-Nakashima K, Shimosaki S, Suekane A, Sarkar B, Saito Y, Ogoh H, Nakahata S, Inoue K, Watanabe T, Nagase H, Morishita K. Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression. Sci Rep. 2018 Sep 13;8(1):13741. doi: 10.1038/s41598-018-32205-8. PMID: 30214063; PMCID: PMC6137133. |
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| 言語 | en | |||||||||||||||
| 書誌情報 |
en : Scientific Reports 巻 8, 号 1, p. 13741, 発行日 2018-09-13 |
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| 出版者 | Springer Nature | |||||||||||||||
| 言語 | en | |||||||||||||||
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| 関連タイプ | isVersionOf | |||||||||||||||
| 識別子タイプ | DOI | |||||||||||||||
| 関連識別子 | https://doi.org/10.1038/s41598-018-32205-8 | |||||||||||||||
| 権利 | ||||||||||||||||
| 権利情報 | © The Author(s) 2018 | |||||||||||||||
| 言語 | en | |||||||||||||||
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| 出版タイプ | VoR | |||||||||||||||
