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DOI | 10.1038/s41467-018-06679-z |
Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells | |
Xu, Yan1,2; Ikeda, Satoshi2; Sumida, Kentaro2; Yamamoto, Ryusuke1,2; Tanaka, Hiroki2; Minato, Nagahiro1,2 | |
2018-03-02 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Japan |
英文摘要 | Chronic myelogenous leukemia (CML) caused by hematopoietic stem cells expressing the Bcr-Abl fusion gene may be controlled by Bcr-Abl tyrosine kinase inhibitors (TKIs). However, CML-initiating cells are resistant to TKIs and may persist as minimal residual disease. We demonstrate that mice deficient in Sipa1, which encodes Rap1 GTPase-activating protein, rarely develop CML upon transfer of primary hematopoietic progenitor cells (HPCs) expressing Bcr-Abl, which cause lethal CML disease in wild-type mice. Resistance requires both T cells and nonhematopoietic cells. Sipa1(-/-) mesenchymal stroma cells (MSCs) show enhanced activation and directed migration to Bcr-Abl(+) cells in tumor tissue and preferentially produce Cxcl9, which in turn recruits Sipa1(-/-) memory T cells that have markedly augmented chemotactic activity. Thus, Sipa1 deficiency uncovers a host immune mechanism potentially capable of eradicating Bcr-Abl(+) HPCs via coordinated interplay between MSCs and immune T cells, which may provide a clue for radical control of human CML. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000426469900016 |
WOS关键词 | CHRONIC MYELOID-LEUKEMIA ; DEREGULATED RAP1 ACTIVATION ; SMALL G-PROTEINS ; STEM-CELLS ; BCR-ABL ; HEMATOPOIETIC PROGENITORS ; SPA-1-DEFICIENT MICE ; MESENCHYMAL CELLS ; RESIDUAL DISEASE ; CANCER |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204055 |
专题 | 资源环境科学 |
作者单位 | 1.Kyoto Univ, Grad Sch Med, Dept Immunol & Cell Biol, Kyoto 6068501, Japan; 2.Kyoto Univ, Grad Sch Med, Med Innovat Ctr, DSK Project, Kyoto 6068501, Japan |
推荐引用方式 GB/T 7714 | Xu, Yan,Ikeda, Satoshi,Sumida, Kentaro,et al. Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Xu, Yan,Ikeda, Satoshi,Sumida, Kentaro,Yamamoto, Ryusuke,Tanaka, Hiroki,&Minato, Nagahiro.(2018).Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells.NATURE COMMUNICATIONS,9. |
MLA | Xu, Yan,et al."Sipa1 deficiency unleashes a host-immune mechanism eradicating chronic myelogenous leukemia-initiating cells".NATURE COMMUNICATIONS 9(2018). |
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