| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-02-19 |
| タイトル |
|
|
タイトル |
Multiple myeloma with t(11;14)-associated immature phenotype has lower CD38 expression and higher BCL2 dependence |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
BCL2 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
CD38 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
daratumumab |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
multiple myeloma |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
venetoclax |
| 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 |
Kitadate, Akihiro
Terao, Toshiki
Narita, Kentaro
Ikeda, Sho
Takahashi, Yuto
Tsushima, Takafumi
Miura, Daisuke
Takeuchi, Masami
Takahashi, Naoto
Matsue, Kosei
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
CD38 expression on myeloma cells is a critical factor affecting the early response to the anti-CD38 antibody daratumumab. However, factors affecting CD38 expression in untreated multiple myeloma are not fully elucidated. In this study, we found that CD38 expression was significantly lower in myeloma patients with the translocation t(11;14)-associated immature plasma cell phenotype, and particularly in those expressing B-cell-associated genes such as PAX5 and CD79A. CD138, a representative marker of plasmacytic differentiation, was also significantly lower in these patients, suggesting that CD38 expression may be associated with the differentiation and maturation stages of myeloma cells. Furthermore, the BCL2/BCL2L1 ratio, a response marker of the BCL2 inhibitor venetoclax, was significantly higher in patients with the immature phenotype expressing B-cell-associated genes. The BCL2/BCL2L1 ratio and CD38 expression were significantly negatively correlated. We also confirmed that patients with translocation t(11;14) expressing B-cell-associated genes were indeed less sensitive to daratumumab-mediated direct cytotoxicity but highly sensitive to venetoclax treatment in ex vivo assays. Moreover, all-trans-retinoic acid, which enhances CD38 expression and induces cell differentiation in myeloma cells, reduced B-cell marker expression and the BCL2/BCL2L1 ratio in myeloma cell lines, leading to reduced efficacy of venetoclax. Venetoclax specifically induces cell death in myeloma with t(11;14), although why patients with translocation t(11;14) show BCL2 dependence is unclear. These results suggest that BCL2 dependence, as well as CD38 expression, are deeply associated with the differentiation and maturation stages of myeloma cells. This study highlights the importance of examining t(11;14) and considering cell maturity in myeloma treatment strategies. |
|
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 9,
p. 3645-3654,
発行日 2021
|
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1347-9032 |
| 出版者 |
|
|
出版者 |
John Wiley and Sons Inc |
| 関連情報 |
|
|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1111/cas.15073 |
| 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. |
iA_2022_39.pdf (1.2 MB)
