ドナー細胞由来白血病発症機構への細胞外小胞の関与の検討

Material type: 文書・図像類

Author: 向田, 直史ほか

Publisher: 金沢大学がん進展制御研究所

Publication date: 2019-06-19

Material Format: Digital

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Note (General)：: BCR-ABL陽性慢性骨髄性白血病（CML)マウスに対して、X線照射・骨髄移植を行うと、核型異常を示すドナー細胞由来顆粒球の出現と重篤な貧血からなる骨髄異形成症候群を呈する、ドナー細胞由来白血病（DCL）を発症した。レシピエントCML細胞由来の細胞外小胞中の大量の二本鎖DNAが、ドナー細胞に水平伝播...

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https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K19681/

https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K19681/17K19681seika/

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Material Type: 文書・図像類
Title: ドナー細胞由来白血病発症機構への細胞外小胞の関与の検討
Author/Editor: 向田, 直史
Mukaida, Naofumi
Author Heading: 向田, 直史
Mukaida, Naofumi
Publication, Distribution, etc.: 金沢大学がん進展制御研究所
Publication Date: 2019-06-19
Publication Date (W3CDTF): 2019-06-19
Alternative Title: Elucidation of the roles of extracellular microsomes in donor cell-derived leukemia
Periodical title: 平成30(2018)年度科学研究費補助金挑戦的研究(萌芽) 研究成果報告書 = 2018 Fiscal Year Final Research Report
No. or year of volume/issue: 2017-06-30 - 2019-03-31
Volume: 2017-06-30 - 2019-03-31
Pages: 6p.-
Text Language Code: jpn
Subject Heading: 骨髄異形成症候群
細胞外小胞
ドナー細胞由来白血病
STING
骨髄移植
BCR-ABL
慢性骨髄性白血病
Target Audience: 一般
Note (General): BCR-ABL陽性慢性骨髄性白血病（CML)マウスに対して、X線照射・骨髄移植を行うと、核型異常を示すドナー細胞由来顆粒球の出現と重篤な貧血からなる骨髄異形成症候群を呈する、ドナー細胞由来白血病（DCL）を発症した。レシピエントCML細胞由来の細胞外小胞中の大量の二本鎖DNAが、ドナー細胞に水平伝播し、ドナー細胞内でSTING経路を介してインターフェロン経路が活性化され、ドナー由来の造血幹/前駆細胞のvitroでの複製能が低下することが明らかになった。さらに、CML発症マウスに対して、X線照射後に、STING欠損マウス由来の骨髄細胞を移植しても、DCL様の病態の出現が認められなかった。
Mice with BCR-ABL-positive chronic myelogenous leukemia (CML) developed donor cell-derived leukemia (DCL), myelodysplastic syndrome with donor cell-derived granulocytes with aberrant nuclear morphology and severe anemia, when normal donor cells were transplanted after irradiation. Recipient leukemia cell-derived extravesicles abundantly contain double-stranded DNA (dsDNA), which was horizontally transmitted into donor cells. In vitro studies demonstrated that dsDNA activated STING and subsequently interferon pathways in donor cells, thereby inhibiting replication capacity of donor hematopoietic stem/progenitor cells. Moreover, CML mice did not develop DCL when they received STING-deficient mouse-derived bone marrow cells after irradiation.
研究課題/領域番号:17K19681, 研究期間(年度):2017-06-30 - 2019-03-31
DOI: 10.24517/00054467
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=30182067
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K19681/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K19681/17K19681seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA