Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression
| العنوان: | Suppression of GPR56 expression by pyrrole-imidazole polyamide represents a novel therapeutic drug for AML with high EVI1 expression |
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| المؤلفون: | Saha, Hasi Rani, 31377, サハ, ハシ ラニ, Kaneda-Nakashima, Kazuko, 34882, 下崎, 俊介, 28595, シモサキ, シュンスケ, Shimosaki, Shunsuke, Suekane, Akira, 34883, Sarkar, Bidhan Chandra, 31376, サルカル, ビードン チャンドラ, Saito, Yusuke, 34318, 小河, 穂波, 34885, オゴウ, ホナミ, Ogoh, Honami, Ogo, Honami, Nakahata, Shingo, 28014, 井上, 健太郎, 30742, イノウエ, ケンタロウ, 80708529, Inoue, Kentaro, Watanabe, Takayoshi, Nagase, Hiroki, Morishita, Kazuhiro, 21835, 森下, 和広, 80260321, モリシタ, カズヒロ |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2018 |
| المجموعة: | University of Miyazaki: Dspace |
| مصطلحات موضوعية: | GPR56 Expression, Ecotropic Viral Integration Site (EVI1), Pyrrole-imidazole Polyamides (PIP), G Protein-coupled Receptors (GPR56), High EVI1 |
| الوصف: | 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. ; 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. ; journal article |
| نوع الوثيقة: | other/unknown material |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | Scientific Reports; 13741; http://hdl.handle.net/10458/0002000435 |
| الاتاحة: | https://miyazaki-u.repo.nii.ac.jp/record/2000435/files/article.pdf http://hdl.handle.net/10458/0002000435 https://miyazaki-u.repo.nii.ac.jp/records/2000435 |
| Rights: | © The Author(s) 2018 |
| رقم الانضمام: | edsbas.6EECB13D |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |