Integrative analysis of epigenome abnormality in the pathogenesis of HTLV-1-associated myelopathy.
| Project/Area Number |
16H05323
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Yamano Yoshihisa 聖マリアンナ医科大学, 医学研究科, 教授 (80445882)
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| Co-Investigator(Kenkyū-buntansha) |
山岸 誠 東京大学, 大学院新領域創成科学研究科, 特任講師 (90625261)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 神経病態免疫学 / HAM / HTLV-1 / エピジェネティクス / エピゲノム操作 / ゲノム操作 |
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| Outline of Final Research Achievements |
The main feature of Human T-cell leukemia virus type I (HTLV-1) -associated myelopathy (HAM) pathogenesis is a virus-induced hyperactive immune response that produces chronic inflammation in the central nervous system (CNS), but the mechanism by which HTLV-1 deregulates the immune response is unknown. We demonstrated that the overexpression of proinflammatory genes such as interferon-gamma, T-bet, C-X-C motif chemokine receptor 3 (CXCR3) were the key difference of HTLV-1 infected cells in patients with HAM compared to those in patients with adult T-cell leukemia/lymphoma (ATL) , a cancer caused by the same HTLV-1 virus that causes HAM. Furthermore, we found that the overexpression of histone methylation enzyme is involved in the acquisition and maintenance of those traits.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、エピゲノム創薬は様々な疾患においても有望視されており、本研究で推進するHTLV-1関連脊髄症（HAM）の病態形成におけるエピゲノム異常の役割に関する解析は、HAMを起点として多くの難病への病態解明や新薬開発にも貴重な情報となり、将来の医療発展にも大きく寄与すると期待される。
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Report
(4 results)
Research Products
(129 results)
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[Journal Article] The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1–associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation2018
Author(s)
Kawano N, Yoshida S, Kawano S, Kuriyama T, Tahara Y, Toyofuku A, Manabe T, Doi A, Terasaka S, Yamashita K, Ueda Y, Ochiai H, Marutsuka K, Yamano Y, Shimoda K, Kikuchi I.
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 58
Issue: 3
Pages: 107-121
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed / Open Access
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[Journal Article] Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity.2018
Author(s)
Sato T, Yagishita N, Tamaki K, Inoue E, Hasegawa D, Nagasaka M, Suzuki H, Araya N, Ariella Coler-Reilly, Hasegawa Y, Tsuboi Y, Takata A, Yamano Y.
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Journal Title
Front Microbiol
Volume: 25(9)
Pages: 1651-1651
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Chronic inflammatory demyelinating polyneuropathy in adult T-cell leukemia-lymphoma patients following allogeneic stem cell transplantation Bone Marrow Transplantation.2018
Author(s)
Hirano M, Jimbo K, Ogawa M, Ochi K, Makiyama J, Kawamata T, Yokoyama K, Tanaka T, Inamoto Y, Yamano Y, Fukuda T, Uchimaru K, Imai Y, Tojo A.
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Journal Title
Bone Marrow Transplantation
Volume: 53
Issue: 11
Pages: 1470-1473
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy.2018
Author(s)
Sato T, Coler-Reilly ALG, Yagishita N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y, Yamano Y.
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Journal Title
N Engl J Med.
Volume: 378(6)
Issue: 6
Pages: 529-538
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effectiveness of Daily Prednisolone to Slow Progression of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Multi-Center Retrospective Cohort Study.2017
Author(s)
Coler-Reilly ALG, Sato T, Matsuzaki T, Nakagawa M, Niino M, Nagai M, Nakamura T, Takenouchi N, Araya N, Yagishita N, Inoue E, Yamano Y.
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Journal Title
Neurotherapeutics
Volume: 14(4)
Issue: 4
Pages: 1084-1094
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Impact of a Humanized CCR4 Antibody (Mogamulizumab) on Patients with Aggressive-Type Adult T-Cell Leukemia-Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation2017
Author(s)
Kawano N, Kuriyama T, Yoshida S, Kawano S, Yamano Y, Marutsuka K, Minato S, Yamashita K, Ochiai H, Shimoda K, Ishikawa F, Kikuchi I.
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Journal Title
Journal of Clinical and Experimental Hematopathology
Volume: 56
Issue: 3
Pages: 135-144
DOI
NAID
ISSN
1346-4280, 1880-9952
Related Report
Peer Reviewed / Open Access
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[Journal Article] Proviral features of human T cell leukemia virus type 1 in carriers with indeterminate western blot analysis results.2017
Author(s)
Kuramitsu M, Sekizuka T, Yamochi T, Firouzi S, Sato T, Umeki K, Sasaki D, Hasegawa H, Kubota R, Sobata R, Matsumoto C, Kaneko N, Momose H, Araki K, Saito M, Nosaka K, Utsunomiya A, Koh K, Ogata M, Uchimaru K, Iwanaga M, Sagara Y, Yamano Y, et al.
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Journal Title
J Clin Microbiol.
Volume: 55(9)
Issue: 9
Pages: 2838-2849
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] IL-10-mediated signals act as a switch for lymphoproliferation in Human T-cell leukemia virus type-1 infection by activating the STAT3 and IRF4 pathways.2017
Author(s)
Sawada L, Nagano Y, Hasegawa A, Kanai H, Nogami K, Ito S, Sato T, Yamano Y, Tanaka Y, Masuda T, Kannagi M.
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Journal Title
PLoS Pathog.
Volume: 13(9)
Issue: 9
Pages: e1006597-e1006597
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reducing the global burden of HTLV-1 infection: An agenda for research and action.2017
Author(s)
Willems L, Hasegawa H, Accolla R, (他10名), Gessain A, Gotuzzo E, Hall W, Harford J, Hermine O, Jacobson S, Macchi B, Macpherson C, Mahieux R, Matsuoka M, Murphy E, Peloponese JM, Simon V, Tagaya Y, Taylor GP, Watanabe T, Yamano Y.
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Journal Title
Antiviral Res
Volume: 137
Pages: 41-48
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Polycomb-dependent epigenetic landscape in adult T-cell leukemia.2016
Author(s)
Dai Fujikawa; Shota Nakagawa; Makoto Hori; Naoya Kurokawa; Ai Soejima; Kazumi Nakano; Tadanori Yamochi; Makoto Nakashima; Seiichiro Kobayashi; Yuetsu Tanaka; Masako Iwanaga; Atae Utsunomiya; Kaoru Uchimaru; Makoto Yamagishi; Toshiki Watanabe
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Journal Title
Blood
Volume: 127
Issue: 14
Pages: 1790-1802
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] NF-kB and JAK-STAT pathways shape transcription landscape in adult T-cell leukemia-lymphoma2018
Author(s)
Yamagishi M, Ishizaki I, Shiga H, Nakano K, Fujikawa D, Kobayashi S, Iwanaga M, Utsunomiya A, Tanaka Y, Watanabe T, Uchimaru K.
Organizer
10th T-cell lymphoma forum
Related Report
Int'l Joint Research
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[Presentation] Daily Prednisolone Slows the Progression of HAM/TSP.2017
Author(s)
Coler-Reilly A, Sato T, MatsuzakiT, Nakagawa M, Niino M, Nagai M, Nakamura T, Takenouchi N, Araya N, Yagishita N, Yamano Y.
Organizer
18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
〔Grand Arc Hanzomon〕東京都千代田区
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Patient Satisfaction Survey for HAM-net Registrants.2017
Author(s)
Suzuki H, Sato K, Kikuchi T, Kimura M, Arifuku H, Komita M, Shimada K, Seki K, Tachibana M, Yagishita N, Coler-Reilly A, Sato T, Araya N, Ishikawa M, Koike M, Saito Y, Takata A, Yamano Y.
Organizer
18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
〔Grand Arc Hanzomon〕東京都千代田区
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Comparative Transcriptome Analysis of HTLV-1-infected Cells and ATL Cells.2017
Author(s)
Yamagishi M, Nakano K, Fujikawa D, Kobayashi S, Araya N, Sato T, Yagishita N, Iwanaga M, Utsunomiya A, Tanaka Y, Yamano Y, Watanabe T, Uchimaru K.
Organizer
18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
〔Grand Arc Hanzomon〕東京都千代田区
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Investigation of Human Leukocyte Antigen on Human T-Lymphotropic Virus Type-1 Associated Myelopathy (HAM) by the Rare Disease Bank.2017
Author(s)
Tada M, Yamano Y, Sato T, Sasaki M, Sakate R, Hinomura A, Hirata M, Tanaka H, Kojima H, Kohara A, Matsuyama A.
Organizer
18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
〔Grand Arc Hanzomon〕東京都千代田区
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] The Development of Human T-cell Leukemia Virus Type 1 (HTLV-1)-Associated Myelopathy (HAM)-Mimicking Myelitis Following Allogeneic Hematopoietic Stem Cell Transplantation for Acute Type Adult T-cell Leukemia-lymphoma (ATL).2017
Author(s)
Kawano N, Yamano Y, Kawano S, Kawamata T, Yoshida S, Kuriyama T, Uchimaru K, Marutsuka K, Minato S, Yamashita K, Ochiai H, Shimoda K, Ishikawa F, Kikuchi I.
Organizer
18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
〔Grand Arc Hanzomon〕東京都千代田区
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Development and Molecular Analysis of Synthetic Lethality by Targeting EZH1/2 in ATL and HTLV-1-infected cells2017
Author(s)
Makoto Yamagishi, Makoto Hori, Dai Fujikawa, Daisuke Honma, Nobuaki Adachi, Takeo Ohsugi, Kazumi Nakano, Makoto Nakashima, Seiichiro Kobayashi, Masako Iwanaga, Atae Utsunomiya, Yuetsu Tanaka, Seiji Okada, Kunihiro Tsukasaki, Kensei Tobinai, Kazushi Araki, Toshiki Watanabe, Kaoru Uchimaru.
Organizer
18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
〔Grand Arc Hanzomon〕東京都千代田区
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Development and molecular analysis of synthetic lethality by targeting EZH1 and EZH2 in T cell lymphomas2017
Author(s)
Makoto Yamagishi, Makoto Hori, Dai Fujikawa, Daisuke Honma, Nobuaki Adachi, Takeo Ohsugi, Kazumi Nakano, Makoto Nakashima, Seiichiro Kobayashi, Masako Iwanaga, Atae Utsunomiya, Seiji Okada, Kunihiro Tsukasaki, Kensei Tobinai, Kazushi Araki, Toshiki Watanabe, Kaoru Uchimaru
Organizer
T-cell Lymphoma Forum 2016
Place of Presentation
San Francisco, CA, U.S.A.
Year and Date
2017-01-26
Related Report
Int'l Joint Research
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[Presentation] Phase 1/2a study of Mogamulizumab, an anti-CCR4 monoclonal antibody, in patients with HTLV-1-associated myelopathy (HAM/TSP).2017
Author(s)
Yamano Y, Sato T, A. Coler-Reilly, Yanagisawa N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y.
Organizer
XXIII World Congress of Neurology
Related Report
Int'l Joint Research
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[Presentation] ＨＴＬＶ－１ プロウイルスＤＮＡ検出キットの臨床的有用性の検討.2017
Author(s)
宮地恵子, 東久世裕太, 小野達也, 永井豪, 篠田達也, 関野久邦, 井上恵, 三浦清徳, 小林誠一郎, 内丸薫, 山野嘉久.
Organizer
第４回日本ＨＴＬＶ－１学会学術集会
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[Presentation] ＡＴＬ患者の同種造血幹細胞移植後に慢性炎症性脱髄性多発ニューロパチーを発症した３症例の解析.2017
Author(s)
平野光人, 今井陽一, 神保光児, 小川弥穂, 越智清純, 川俣豊隆, 横山和明, 大野伸広, 山野嘉久, 福田隆浩, 内丸薫, 東條有伸.
Organizer
第４回日本ＨＴＬＶ－１学会学術集会
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[Presentation] Tumor cell-of-origin and mutation landscape for EZH1/2 targeting precision therapy2017
Author(s)
Yamagishi M, Fujikawa D, Hori M, Honma D, Adachi N, Iwanaga M, Utsunomiya A, Okada S, Tsukasaki K, Tobinai K, Araki K, Watanabe T, Uchimaru K.
Organizer
第76回日本癌学会学術総会
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[Presentation] Development and molecular analysis of synthetic lethality by targeting EZH1 and EZH2 in malignant lymphomas2017
Author(s)
Yamagishi M, Hori M, Fujikawa D, Honma D, Adachi N, Ohsugi T, Nakano K, Nakashima M, Kobayashi S, Iwanaga M, Utsunomiya A, Okada S, Tsukasaki K, Tobinai K, Araki K, Watanabe T, Uchimaru K.
Organizer
第79回日本血液学会学術集会
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[Presentation] EZH1/2, SWI/SNF, and MLL2 dependent heterochromatin formation and abnormal transcriptome in hematological malignancies2017
Author(s)
Yamagishi M, Fujikawa D, Hori M, Honma D, Adachi N, Kobayashi S, Iwanaga M, Utsunomi ya A, Okada S, Tsukasaki K, Tobinai K, Araki K, Watanabe T, Uchimaru K.
Organizer
59th ASH Annual Meeting
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Author(s)
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Organizer
the 58th ASH Annual Meeting and Exposition
Place of Presentation
San Diego, CA, U.S.A.
Year and Date
2016-12-03
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