The pathogenesis of myeloproliferative neoplasms induced by TET2 mutation
| Project/Area Number |
26461408
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 骨髄増殖性腫瘍 / TET2 / JAK2 |
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| Outline of Final Research Achievements |
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 MPNs, and the addition of loss-of-TET2 worsened this JAK2V617F-induced disease. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the 2nd recipients, which did not develop MPNs. In contrast, cooperation between JAK2V617F and loss-of-TET2 developed and maintained MPNs in the 2nd recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. 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; one is as a disease accelerator, while the other is as a disease initiator and sustainer in combination with JAK2V617F.
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Effects of mogamulizumab in adult T-cell leukemia/lymphoma in clinical practice.2017
Author(s)
Sekine M, Kubuki Y, Kameda T, Takeuchi M, Toyama T, Kawano N, Maeda K, Sato S, Ishizaki J, Kawano H, Kamiunten A, Akizuki K, Tahira Y, Shimoda H, Shide K, Hidaka T, Kitanaka A, Yamashita K, Matsuoka H, Shimoda K
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Journal Title
European journal of haematology.
Volume: 98
Issue: 5
Pages: 501-507
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Differences in Hematological and Clinical Features Between Essential Thrombocythemia Cases With JAK2- or CALR-Mutations.2017
Author(s)
Kubuki Y, Shide K, Kameda T, Yamaji T, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Hashimoto K, Yamamoto S, Hasuike S, Hidaka T, Nagata K, Kitanaka A, Shimoda K
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Journal Title
Annals of laboratory medicine.
Volume: 37
Issue: 2
Pages: 159-161
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] <i>TET2</i> mutation in diffuse large B-cell lymphoma2017
Author(s)
Kubuki Y, Yamaji T, Hidaka T, Kameda T, Shide K, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A, Shimoda K
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 56
Issue: 3
Pages: 145-149
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed
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[Journal Article] Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib2016
Author(s)
Kotaro Shide, Takuro Kameda, Takumi Yamaji, Masaaki Sekine, Naoki Inada, Ayako Kamiunten, Keiichi Akizuki, Kenichi Nakamura, Akira Kitanaka, Arata Honda, Akira Sawaguchi, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Satoru Hasuike, Shojiro Yamamoto, Kenji Nagata, and Kazuya Shimoda
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Journal Title
Leukemia
Volume: 31
Issue: 5
Pages: 1136-1144
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TET2 Mutation in Adult T-Cell Leukemia/Lymphoma2015
Author(s)
Shimoda K, Shide K, Kameda T, Hidaka T, Kubuki Y, Kamiunten A, Sekine M, Akizuki K, Shimoda H, Yamaji T, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 55
Issue: 3
Pages: 145-149
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms.2015
Author(s)
Kameda T, Shide K, Yamaji T, Kamiunten A, Sekine M, Hidaka T, Kubuki Y, Sashida G, Aoyama K, Yoshimitsu M, Abe H, Miike T, Iwakiri H, Tahara Y, Yamamoto S, Hasuike S, Nagata K, Iwama A, Kitanaka A, Shimoda K
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Journal Title
Genom Data.
Volume: 4
Pages: 102-108
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator.2015
Author(s)
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.
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Journal Title
Blood
Volume: 125
Issue: 2
Pages: 304-315
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] Mogamulizumab for adult T-cell leukemia/lymphoma in clinical practice.2016
Author(s)
Masaaki Sekine, Yoko Kubuki, Takuro Kameda, Masaki Takeuchi, Takanori Toyama, Noriaki Kawano, Kouichi Maeda, Siichi Sato, Junzo Ishizaki, Hiroshi Kawano, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Haruko Shimoda, Kotaro Shide, Tomonori Hidaka, Akira Kitanaka, Kiyoshi Yamashita, Hitoshi Matsuoka, Kazuya Shimoda
Organizer
58th ASH Annual Meeting & Exposition
Place of Presentation
サンディエゴ（アメリカ合衆国)
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Physiological Expression of Calr Mutant Increases Cell Growth and Cytokine Independency in Human Cell Lines Expressing Mpl, and Develops Essential Thrombocythemia in Mice.2016
Author(s)
Kotaro Shide, Takuro Kameda, Masaaki Sekine, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Tomonori Hidaka, Yoko Kubuki, Arata Honda, Akira Sawaguchi, Akira Kitanaka, Kazuya Shimoda
Organizer
58th ASH Annual Meeting & Exposition
Place of Presentation
サンディエゴ（アメリカ合衆国)
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] CALRdel52 mutation activates the JAK-STAT pathway in coordination with MPL, and causes ET in mice.2016
Author(s)
Kotaro Shide, Takuro Kameda, Masaaki Sekine, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Haruko Shimoda, Tomonori Hidaka, Yoko Kubuki, Arata Honda, Akira Kitanaka, Kazuya Shimoda
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜(横浜市)
Year and Date
2016-10-15
Related Report
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[Presentation] Loss-of-TET2 induces clonal expansion of JAK2V617F mutant stem/progenitor cell and initiates MPNs2014
Author(s)
Kamada T,Shide K, Akizuki K, Sekine M, Kamiunten A, Shimoda H, Hidaka T, Kubuki Y, Kitanaka A, Marutsuka K, Shimoda K
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪市
Year and Date
2014-10-31 – 2014-11-02
Related Report
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[Book] 難病事典2015
Author(s)
北中明、下田和哉
Total Pages
511
Publisher
株式会社学研メディカル秀潤社
Related Report
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