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Impact of hypoxia on the pathogenesis and therapy resistance in multiple myeloma
http://hdl.handle.net/10295/00006159
http://hdl.handle.net/10295/00006159f5586aca-d3f1-4bbc-9acd-15ed78355f33
名前 / ファイル | ライセンス | アクション |
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2023-02-18 | |||||
タイトル | ||||||
タイトル | Impact of hypoxia on the pathogenesis and therapy resistance in multiple myeloma | |||||
言語 | en | |||||
言語 | ||||||
言語 | eng | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | HIF | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | hypoxia | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | IRF4 | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | multiple myeloma | |||||
主題 | ||||||
主題Scheme | Other | |||||
主題 | MYC | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
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 | |||||
作成者 |
Ikeda, Sho
× Ikeda, Sho× Tagawa, Hiroyuki |
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内容記述 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Multiple myeloma (MM) is a refractory plasma cell tumor. In myeloma cells, the transcription factor IRF4, the master regulator of plasma cells, is aberrantly upregulated and plays an essential role in oncogenesis. IRF4 forms a positive feedback loop with MYC, leading to additional tumorigenic properties. In recent years, molecular targeted therapies have contributed to a significant improvement in the prognosis of MM. Nevertheless, almost all patients experience disease progression, which is thought to be a result of treatment resistance induced by various elements of the bone marrow microenvironment. Among these, the hypoxic response, one of the key processes for cellular homeostasis, induces hypoxia-adapted traits such as undifferentiation, altered metabolism, and dissemination, leading to drug resistance. These inductions are caused by ectopic gene expression changes mediated by the activation of hypoxia-inducible factors (HIFs). By contrast, the expression levels of IRF4 and MYC are markedly reduced by hypoxic stress. Notably, an anti-apoptotic capability is usually acquired under both normoxic and hypoxic conditions, but the mechanism is distinct. This fact strongly suggests that myeloma cells may survive by switching their dependent regulatory factors from IRF4 and MYC (normoxic bone marrow region) to HIF (hypoxic bone marrow microenvironment). Therefore, to achieve deep remission, combination therapeutic agents, which are complementarily effective against both IRF4-MYC-dominant and HIF-dominated fractions, may become an important therapeutic strategy for MM. | |||||
言語 | en | |||||
出版タイプ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
書誌情報 |
en : Cancer Science 巻 112, 号 10, p. 3995-4004, 発行日 2021 |
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収録物識別子 | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 13479032 | |||||
出版者 | ||||||
出版者 | John Wiley and Sons Inc | |||||
関連情報 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1111/cas.15087 | |||||
権利情報 | ||||||
権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |