Integrated analysis of abnormal expression profiles that define phenotype of ATL cells
| Project/Area Number |
26293226
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | St. Marianna University School of Medicine (2016)
The University of Tokyo (2014-2015) |
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Principal Investigator |
Watanabe Toshiki 聖マリアンナ医科大学, 医学(系)研究科(研究院), 教授 (30182934)
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| Co-Investigator(Kenkyū-buntansha) |
内丸 薫 東京大学, 医科学研究所, 准教授 (60251203)
中野 和民 東京大学, 新領域創成科学研究科, 助教 (60549591)
矢持 忠徳 東京大学, 新領域創成科学研究科, 特任研究員 (80306844)
山岸 誠 東京大学, 新領域創成科学研究科, 特任助教 (90625261)
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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 |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 血液腫瘍学 / ゲノム機能発現 |
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| Outline of Final Research Achievements |
To decipher the molecular characteristics of adult T cell leukemia-lymphoma (ATL) and HTLV-1 infected cells, we conducted whole gene expression analysis, epigenome analysis, comprehensive splicing pattern analysis, and translatome analysis. We found that (1) epigenetic abnormality and its biological impact on gene expression, (2) abnormal splicing pattern involved in the leukemogenesis, (3) promoted translation efficiency in acute phase, and (4) persistent activation of signaling pathways including NF-κB, Hedgehog, and TAK1-p38. We also identified some promising molecules for clinical targeting and biomarker. The identified aberrant “quality” and “quantity” of the gene expression pattern appears to be involved in the pathogenesis and development of ATL.
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Report
(4 results)
Research Products
(46 results)
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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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[Journal Article] Advanced HTLV-1 carriers and early-stage indolent ATLs are indistinguishable based on CADM1 positivity in flow cytometry2015
Author(s)
Kobayashi S, Watanabe E, Ishigaki T, Ohno N, Yuji K, Nakano K, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K.
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Journal Title
Cancer Sci
Volume: 印刷中
Issue: 5
Pages: 598-603
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of TL-Om1, an ATL Cell Line, as a Reference Material for Human T-Lymphotropic Virus 1 Quantitative PCR.2015
Author(s)
Kuramitsu M, Okuma K, Yamagishi M, Yamochi T, Firouzi S, Momose H, Mizukami T, Takizawa K, Araki K, Sugamura K, Yamaguchi K, Watanabe T, Hamaguchi I.
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Journal Title
Journal of Clinical Microbiology
Volume: 53
Issue: 2
Pages: 587-596
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-I-infected cells in adult T-cell leukemia/lymphoma2014
Author(s)
Kobayashi S, Nakano K, Watanabe E, Ishigaki T, Ohno N, Yuji K, Oyaizu N, Asanuma S, Yamagishi M, Yamochi T, Watanabe N, Tojo A, Watanabe T, Uchimaru K
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Journal Title
Clinical Cancer Research
Volume: 20(11)
Issue: 11
Pages: 2851-61
DOI
Related Report
Peer Reviewed / Open Access
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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)
Yamagishi M, Hori M, Fujikawa D, Honma D, Adachi N, Ohsugi T, Nakano K, Nakashima M, Kobayashi S, Iwanaga M, Utsunomiya A, Tanaka Y, Okada S, Tsukasaki K, Tobinai K, Araki K, Watanabe T, Uchimaru K
Organizer
18th International Conference on Human Retrovirology：HTLV and Related Viruses
Place of Presentation
Hotel Grand Ark Hanzomon, Tokyo
Year and Date
2017-03-10
Related Report
Int'l Joint Research
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[Presentation] Comparative Transcriptome Analysis of HTLV-1-infected cells and ATL cells2017
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
Hotel Grand Ark Hanzomon, Tokyo
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)
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
9th Annual T-Celll Lymphoma Forum
Place of Presentation
San Francisco, CA, U.S.A.
Year and Date
2017-01-28
Related Report
Int'l Joint Research
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[Presentation] Development and Molecular Analysis of Synthetic Lethality By Targeting EZH1 and EZH2 in Non-Hodgkin Lymphomas2016
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
the 58th ASH Annual Meeting and Exposition
Place of Presentation
San Diego, CA, U.S.A.
Year and Date
2016-12-04
Related Report
Int'l Joint Research
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[Presentation] Polycomb-dependent epigenetic landscape in adult T cell leukemia (ATL); providing proof of concept for targeting EZH1/2 to selectively eliminate the HTLV-1 infected population2016
Author(s)
Yamagishi M, Fujikawa D, Ohsugi T, Honma D, Adachi N, Nakagawa S, Hori M, Kurokawa N, Soejima A, Nakano K, Yamochi T, Nakashima M, Kobayashi S, Tanaka Y, Iwanaga M, Utsunomiya A, Uchimaru K, Tsukasaki K, Araki K, Watanabe T
Organizer
T-cell Lymphoma Forum 2016
Place of Presentation
San Francisco, CA, U.S.A.
Year and Date
2016-01-29
Related Report
Int'l Joint Research
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[Presentation] Polycomb-Dependent Epigenetic Landscape in Adult T Cell Leukemia (ATL); Providing Proof of Concept for Targeting EZH1/2 to Selectively Eliminate the HTLV-1 Infected Population2015
Author(s)
Yamagishi M, Fujikawa D, Honma D, Adachi N, Nakagawa S, Hori M, Kurokawa N, Soejima A, Nakano K, Yamochi T, Nakashima M, Kobayashi S, Tanaka Y, Iwanaga M, Utsunomiya A, Uchimaru K, Tsukasaki K, Araki K, Watanabe T
Organizer
the 57th ASH Annual Meeting and Exposition
Place of Presentation
Orlando, FL, U.S.A.
Year and Date
2015-12-07
Related Report
Int'l Joint Research
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[Presentation] EZH2-dependent epigenetic landscape in adult T-cell leukemia and Tax-immortalized cells2015
Author(s)
Fujikawa D, Yamagishi M, Nakagawa S, Kurokawa N, Soejima A, Kobayashi S, Uchimaru K, Tanaka Y, Nakano K, Watanabe T
Organizer
17th Internatioal Conference on Human Retrovilrology HTLV & Related Viruses
Place of Presentation
the Carayou Hotel, Martinique, France
Year and Date
2015-06-19
Related Report
Int'l Joint Research
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[Presentation] Landscape of genetic alterations in adult T-cell leukemia/lymphoma2014
Author(s)
Kataoka K, Nagata Y, Kitanaka A, Sato-Otsubo A, Totoki Y, Yasunaga J, Sanada M, Shiraishi Y, Chiba K, Tanaka H, Suzuki H, Sato Y, Shiozawa Y, Yoshizato T, Kon A, Yoshida K, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Watanabe T（35人中31番目）, Ogawa S
Organizer
56th of ASH Annual Meeting and Exposition
Place of Presentation
Moscone Center, San Francisco, U.S.A.
Year and Date
2014-12-07
Related Report
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[Presentation] Novel Biological Effects and Distinct Patterns of Rhoa Mutations in Adult T-Cell Leukemia/Lymphoma and Angioimmunoblastic T Cell Lymphoma2014
Author(s)
Nagata Y, Enami T, Kontani K, Kataoka K, Sakata-Yanagimoto M, Kitanaka A, Sato A, Shiraishi Y, Chiba K, Tanaka H, Shiozawa Y, Yoshizato T, Kon A, Yoshida K, Sanada M, Ishiyama K, Miyawaki S, Ishii R, Nureki O, Miyano S, Shimoda K, Watanabe T, Katada T, Chiba S, Ogawa S
Organizer
56th of ASH Annual Meeting and Exposition
Place of Presentation
Moscone Center, San Francisco, U.S.A.
Year and Date
2014-12-07
Related Report
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[Presentation] Tumor-specific gene expression leads to p38 and Hedgehog signaling activation in adult T cell leukemia2014
Author(s)
Yamagishi M, Takahashi R, Sakai N, Fujikawa D, Nakagawa S, Yamochi T, Yamochi T, Nakano K, Uchimaru K, Utsunomiya A, Watanabe T
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場、大阪
Year and Date
2014-11-01
Related Report
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[Presentation] Distinct patterns of RHOA mutations in Adult T-Cell Leukemia/Lymphoma and peripheral T-Cell lymphomas2014
Author(s)
Nagata Y, Enami T, Sakata-Yanagimoto M, Kataoka K, Kitanaka A, Sato A, Shiraishi Y, Chiba K, Tanaka H, Shiozawa Y, Yoshizato T, Kon A, Yoshida K, Sanada M, Ishiyama K, Miyawaki S, Ishii R, Nureki O, Miyano S, Shimoda K, Watanabe T, Chiba S, Ogawa S
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場、大阪
Year and Date
2014-11-01
Related Report
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[Presentation] Landscape of genetic alterations in adult T-cell leukemia/lymphoma2014
Author(s)
Kataoka K, Nagata Y, Kitanaka A, Sato-Otsubo A, Totoki Y, Yasunaga J, Sanada M, Shiraishi Y, Chiba K, Tanaka H, Suzuki H, Sato Y, Shiozawa Y, Yoshizato T, Kon A, Yoshida K, Munakata W, Nakamura H, Hama N, Shide K, Kubuki Y, Watanabe T（35人中31番目）, Ogawa S
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場、大阪
Year and Date
2014-11-01
Related Report
