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Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator
http://hdl.handle.net/10458/5439
http://hdl.handle.net/10458/5439ec3bedc6-de08-44b6-a8a4-28f2947eae11
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2020-06-21 | |||||
| タイトル | ||||||
| タイトル | Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| 著者 |
亀田, 拓郎
× 亀田, 拓郎× 幣, 光太郎× 山路, 卓巳× 上運天, 綾子× 関根, 雅明× Taniguchi, Yasuhiro× 日髙, 智徳× 久冨木, 庸子× 下田, 晴子× 丸塚, 浩助× Sashida, Goro× Aoyama, Kazumasa× Yoshimitsu, Makoto× 原田, 拓× 安倍, 弘生× 三池, 忠× 岩切, 久芳× 田原, 良博× 末田, 光恵× 山本, 章二朗× 蓮池, 悟× 永田, 賢治× Iwama, Atsushi× 北中, 明× 下田, 和哉 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss of TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss of TET2 developed and maintained MPNs in the second recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long-term, but concurrent loss of TET2 mutation restored it. Transcriptional profiling revealed that loss of TET2 affected the expression of many HSC signature genes. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: Kameda T, Shide K, Yamaji T, Kamiunten A, Sekine M, Taniguchi Y, Hidaka T, Kubuki Y, Shimoda H, Marutsuka K, Sashida G, Aoyama K, Yoshimitsu M, Harada T, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Iwama A, Kitanaka A, Shimoda K. Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator. Blood. 2015 Jan 8;125(2):304-15. doi: 10.1182/blood-2014-04-555508. Epub 2014 Nov 13. PMID: 25395421. |
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| 言語 | en | |||||
| 書誌情報 |
en : Blood 巻 125, 号 2, p. 304-315, 発行日 2015-01-08 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| 言語 | en | |||||
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| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0006-4971 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1182/blood-2014-04-555508 | |||||
