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RLTPR Q575E : 成人T細胞白血病/リンパ腫における新規反復性機能獲得型変異
http://hdl.handle.net/10232/00031696
http://hdl.handle.net/10232/00031696700d86ac-72e2-4e56-bea0-145022a4c1fd
| 名前 / ファイル | ライセンス | アクション |
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Diss_内田_友一朗_4516800024_2020 (750.1 kB)
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Abstract_内田_友一朗_4516800024_2020 (232.6 kB)
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Result_Uchida_Yuichiro_isk_581 (223.0 kB)
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Comments_Uchida_Yuichiro_isk_581 (101.4 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-04-09 | |||||
| タイトル | ||||||
| タイトル | RLTPR Q575E : A novel recurrent gain-of-function mutation in patients with adult T-cell leukemia/lymphoma | |||||
| タイトル言語 | en | |||||
| タイトル | ||||||
| タイトル | RLTPR Q575E : 成人T細胞白血病/リンパ腫における新規反復性機能獲得型変異 | |||||
| タイトル言語 | ja | |||||
| 著者 |
内田, 友一朗
× 内田, 友一朗 |
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| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | adult T-cell leukemia/lymphoma | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | gain-of-function mutation | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | NF-κB signaling | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | RLTPR Q575E | |||||
| キーワード | ||||||
| 主題言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | T-cell receptor signaling | |||||
| 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 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Objectives: Adult T-cell leukemia/lymphoma (ATL) is an intractable T-cell malignancy caused by long-term infection with human T-cell leukemia virus type-1 (HTLV-1). While ATL pathogenesis has been associated with HTLV-1-derived oncogenic proteins, including Tax and HBZ, the contribution of genomic aberrations remains poorly defined. Methods: To elucidate the genomic basis of ATL, whole exome sequencing was performed on cells from 47 patients with aggressive ATL. Results: We discovered the novel mutation RLTPR Q575E in four patients (8.5%) with a median variant allele frequency of 0.52 (range 0.11-0.68). Despite being reported in cutaneous T-cell lymphoma, three ATL patients carrying RLTPR Q575E lacked skin involvement. Patients carrying RLTPR Q575E also harbored CARD11 (75%), PLCG1 (25%), PRKCB (25%), or IKBKB (25%) mutations related to TCR/NF-κB signaling. Jurkat cells transfected with RLTPR Q575E cDNA displayed increased NF-κB activity and significantly increased IL-2 mRNA levels under stimulation. RLTPR Q575E increased the interaction between RLTPR and CARD11, while RLTPR directly interacted with Tax. Conclusions: We identified, and functionally validated, a novel gain-of-function mutation in patients with aggressive ATL. During TCR activation by Tax or gain-of-function mutations, RLTPR Q575E selectively upregulates NF-κB signaling and may exert oncogenic effects on ATL pathogenesis. This is the peer reviewed version of the following article: Yuichiro Uchida, Makoto Yoshimitsu, Miho Hachiman, Shuichi Kusano, Naosuke Arima, Kodai Shima, Maiko Hayashida, Yuhei Kamada, Daisuke Nakamura, Akihiko Arai, Yuetsu Tanaka, Hiromitsu Hara, Kenji Ishitsuka RLTPR Q575E: A novel recurrent gain-of-function mutation in patients with adult T-cell leukemia/lymphoma European Journal of Haematology (2021), 106(2), 221–229 © 2020 John Wiley & Sons A/S. which has been published in final form at https://doi.org/10.1111/ejh.13540 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2021-02-09 | |||||
| 日付タイプ | Collected | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| NDC | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 490 | |||||
| ファイル（説明） | ||||||
| 内容記述 | 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 | |||||
| 公開者・出版者 | ||||||
| 出版者 | John Wiley & Sons Ltd | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 公開者・出版者 | ||||||
| 出版者 | カゴシマ ダイガク | |||||
| 出版者言語 | ja-Kana | |||||
| 備考 | ||||||
| 備考 | 【指導教員:石塚賢治】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2020-12-02 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 学位授与機関名 | 鹿児島大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2021-02-25 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲総研第581号 | |||||
