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Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL -mediated leukemia
http://hdl.handle.net/10076/0002000842
http://hdl.handle.net/10076/00020008423b83870e-9b66-4c93-b9d2-ba7de5ec6ffe
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
2024DM0710.pdf (4.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||
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| 公開日 | 2024-07-29 | |||||||||||
| タイトル | ||||||||||||
| タイトル | Bahcc1 is critical for the aberrant epigenetic program in a mouse model of MLL-ENL -mediated leukemia | |||||||||||
| 言語 | en | |||||||||||
| 言語 | ||||||||||||
| 言語 | eng | |||||||||||
| 資源タイプ | ||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||
| 資源タイプ | doctoral thesis | |||||||||||
| アクセス権 | ||||||||||||
| アクセス権 | open access | |||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||
| 著者 |
中村, 彰秀
× 中村, 彰秀
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| 抄録 | ||||||||||||
| 内容記述タイプ | Abstract | |||||||||||
| 内容記述 | In leukemogenesis, genotoxic stress in hematopoietic stem and progenitor cells (HSPCs) drives individual context-dependent programs of malignant transformation. In light of the various differentiation stages of HSPCs based on a recently revised definition using CD150/CD48, our analyses showed that a subpopulation of long-term repopulating HSCs was most susceptible to MLL-ENL–mediated transformation. An analysis of the molecular mechanism identified Bromo-adjacent homology domain and coiled-coil containing 1 (Bahcc1), which encodes a reader molecule of trimethylated histone H3 lysine 27 (H3K27me3), as a candidate gene involved in distinct susceptibility to leukemic transformation. Interestingly, Bahcc1 was previously reported to be highly expressed in acute myeloid leukemia (AML) with an unfavorable prognosis, including some cases of MLL-rearranged AML. We found that MLL-ENL upregulated Bahcc1 through binding to its promoter, and that Bahcc1 was involved in MLL-ENL–mediated immortalization at least partly through repression of H3K27me3-marked Cdkn1c. Analyses using bone marrow transplantation in mice showed that depletion of Bahcc1 suppressed the leukemogenic activity of MLL-ENL. In a public database, high BAHCC1 expression was found to be associated with a poor prognosis in pediatric AML, in which BAHCC1 expression was significantly lower in MLL-AF9-AML than in other MLL-fusion-AML. These findings shed light on the distinct immortalization potential of HSPCs and suggest a novel MLL-fusion-Bahcc1 axis, which may lead to development of molecular targeted therapy against MLL-fusion–mediated leukemia. | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 本文/Department of Microbiology and Molecular Genetics and Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan | |||||||||||
| 内容記述 | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | 30p | |||||||||||
| 書誌情報 |
発行日 2024-07-17 |
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| DOI | ||||||||||||
| 識別子タイプ | DOI | |||||||||||
| 関連識別子 | 10.1182/ bloodadvances.2023011320. | |||||||||||
| フォーマット | ||||||||||||
| 内容記述タイプ | Other | |||||||||||
| 内容記述 | application/pdf | |||||||||||
| 出版者 | ||||||||||||
| 出版者 | 三重大学 | |||||||||||
| 出版者（ヨミ） | ||||||||||||
| ミエダイガク | ||||||||||||
| 学位名 | ||||||||||||
| 学位名 | 博士(医学) | |||||||||||
| 学位授与機関 | ||||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||||
| 学位授与機関識別子 | 14101 | |||||||||||
| 学位授与機関名 | 三重大学 | |||||||||||
| 学位授与年月日 | ||||||||||||
| 学位授与年月日 | 2024-07-17 | |||||||||||
| 学位授与番号 | ||||||||||||
| 学位授与番号 | 甲医学第2273号 | |||||||||||
| ノート | ||||||||||||
| 資源タイプ（三重大） | ||||||||||||
| Doctoral Dissertation / 博士論文 | ||||||||||||
