論文 - 詳細
| RRC ID | 56051 |
|---|---|
| 著者 | Ichii M, Oritani K, Murase M, Komatsu K, Yamazaki M, Kyoden R, Kito N, Nozaki Y, Saito M, Iwamura H, Kanakura Y. |
| タイトル | Molecular targeting of inosine-5'-monophosphate dehydrogenase by FF-10501 promotes erythropoiesis via ROS/MAPK pathway. |
| ジャーナル | Leuk Lymphoma |
| Abstract |
One of the major symptoms of myelodysplastic syndromes (MDS) is severe cytopenia. Despite cytokine therapies, such as erythropoiesis-stimulating agents, many patients still require blood transfusions, and the development of new therapeutic approaches is needed. In this work, we studied the effects of the inosine-5'-monophosphate (IMP) dehydrogenase (IMPDH) inhibitor FF-10501 on erythropoiesis of human hematopoietic cells. Differentiation of K562 chronic myeloid leukemia cells to an erythroid lineage was promoted by FF-10501 in a dose-dependent manner. Interestingly, we found that metabolic conversion of IMP to hypoxanthine leads to elevation of reactive oxygen species (ROS). The differentiative effects of FF-10501 were abolished by the ROS scavenger dimethylthiourea or the p38 MAPK inhibitor SB203580. Furthermore, FF-10501 promoted erythropoiesis from CD34+ hematopoietic stem/progenitor cells, accompanied with ROS accumulation, while high-dose FF-10501 mainly showed cytotoxic effects. These findings denote the potential of IMPDH inhibition therapy with FF-10501 in amelioration of anemia in MDS patients. |
| 巻・号 | 59(2) |
| ページ | 448-459 |
| 公開日 | 2018-2-1 |
| DOI | 10.1080/10428194.2017.1339878 |
| PMID | 28730859 |
| MeSH | Apoptosis / drug effects Bone Marrow Cells / cytology Bone Marrow Cells / drug effects Bone Marrow Cells / metabolism Case-Control Studies Cell Cycle / drug effects Cell Differentiation / drug effects Cell Line, Tumor Cell Lineage / drug effects Cell Proliferation / drug effects Enzyme Inhibitors / pharmacology* Erythropoiesis / drug effects* Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / drug effects Hematopoietic Stem Cells / metabolism Humans IMP Dehydrogenase / antagonists & inhibitors* MAP Kinase Signaling System / drug effects* Myelodysplastic Syndromes Phagocytosis / drug effects Phagocytosis / immunology Reactive Oxygen Species / metabolism* |
| IF | 2.674 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | K562(RCB0027) HL60 Jurkat RPMI8226(RCB3010) Raji |