| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2019-09-25 |
| タイトル |
|
|
タイトル |
Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target |
| 言語 |
|
|
言語 |
eng |
| DOI |
|
|
|
関連識別子 |
https://doi.org/10.1038/s41467-018-03987-2 |
|
|
関連名称 |
10.1038/s41467-018-03987-2 |
| 資源タイプ |
|
|
資源 |
http://purl.org/coar/resource_type/c_6501 |
|
タイプ |
journal article |
| 著者 |
Dufva, Olli
Kankainen, Matti
Kelkka, Tiina
Sekiguchi, Nodoka
Awad, Shady Adnan
Eldfors, Samuli
Yadav, Bhagwan
Kuusanmaki, Heikki
Malani, Disha
Andersson, Emma I.
Pietarinen, Paavo
Saikko, Leena
Kovanen, Panu E.
Ojala, Teija
Lee, Dean A.
Loughran, Thomas P. Jr.
Nakazawa, Hideyuki
Suzumiya, Junji
Suzuki, Ritsuro
Ko, Young Hyeh
Kim, Won Seog
Chuang, Shih-Sung
Aittokallio, Tero
Chan, Wing C.
Ohshima, Koichi
Ishida, Fumihiro
Mustjoki, Satu
|
| 信州大学研究者総覧へのリンク |
|
|
氏名 |
Nakazawa, Hideyuki |
|
URL |
http://soar-rd.shinshu-u.ac.jp/profile/ja.yeSagpkh.html |
| 信州大学研究者総覧へのリンク |
|
|
氏名 |
Ishida, Fumihiro |
|
URL |
http://soar-rd.shinshu-u.ac.jp/profile/ja.ueTCHhkh.html |
| 出版者 |
|
|
出版者 |
NATURE PUBLISHING GROUP |
| 引用 |
|
|
内容記述 |
NATURE COMMUNICATIONS.9:1567(2018) |
| 書誌情報 |
NATURE COMMUNICATIONS
巻 9,
p. 1567,
発行日 2018-04-19
|
| 抄録 |
|
|
内容記述 |
Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data. Drug sensitivity profiling further demonstrates the role of the JAK-STAT pathway in the pathogenesis of NK-cell malignancies, identifying NK cells to be highly sensitive to JAK and BCL2 inhibition compared to other hematopoietic cell lineages. Our results provide insight into ANKL genetics and a framework for application of targeted therapies in NK-cell malignancies. |
| 資源タイプ（コンテンツの種類） |
|
| ISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
2041-1723 |
| 書誌レコードID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12645905 |
| PubMed |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
https://www.ncbi.nlm.nih.gov/pubmed/29674644 |
|
|
関連名称 |
29674644 |
| 権利 |
|
|
権利情報 |
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| WoS |
|
|
URL |
http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000430389400002 |
15K09471_01.pdf (1.2 MB)
