Oncogene addiction of ATL cells and abnormal Polycomb-miRNA-signal transduction
| Project/Area Number |
23390250
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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 |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
UCHIMARU Kaoru 東京大学, 医科学研究所, 准教授 (60251203)
NAKANO Kazumi 東京大学, 大学院・新領域創成科学研究科, 助教 (60549591)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2011: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | 血液腫瘍学 / HTLV-1 / NP-κB / エピジェネティクス / シグナル伝達 / NF-κB |
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| Research Abstract |
Based on our comprehensive dataset from ATL patient samples, we addressed the exact molecular mechanism of ATL, which should be targeted in clinical regimens. Using a microarray technique, we identified leukemic cell-specific gene expression pattern. In addition, we revealed activation of p38 and Hedgehog signaling pathways, which supported pro-survival capability.
We performed global histone methylation profiling of patient-derived primary ATL cells. We successfully detected the numerous gene promoters with aberrant repressive H3K27me3 mark in ATL cells. Interestingly, Tax-triggered immortalizing cells partially mimicked the methylation pattern observed in ATL cells. In parallel, we identified an intimate relationship between NF-kB signaling and EZH2. Despite the absence of EZH2 active mutation observed in DLBCL, EZH2 inhibitors significantly killed patient ATL cells. Our findings indicate that ATL is characterized by EZH2-dependent robust and global epigenetic rearrangement.
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Report
(4 results)
Research Products
(108 results)
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[Journal Article] CADM1 expression and stepwise downregulation of CD7 are closely associated with clonal expansion of HTLV-1-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
Clin Cancer Res
Volume: (in press)
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Peer Reviewed
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[Journal Article] Meeting report on the possible proposal of an extra-nodal primary cutaneous variant in the lymphoma type of adult T-cell leukemia-lymphoma2014
Author(s)
Tsukasaki K, Imaizumi Y, Tokura Y, Ohshima K, Kawai K, Utsunomiya A, Amano M, Watanabe T, Nakamura S, Iwatsuki K, Kamihira S, Yamaguchi K, Shimoyama M
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Journal Title
J Dermatol
Volume: 41(1)
Issue: 1
Pages: 26-28
DOI
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Peer Reviewed
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[Presentation] Molecular hallmarks of adult T cell leukemia : miRNA, pigenetics, and emerging signaling abnormalities2013
Author(s)
Yamagishi M, Fujikawa D, Kurokawa N, Soejima A, Takahashi R, Sakai N, Nakagawa S, Nakano K, Kobayashi S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
Organizer
16th International Conference on Human Retrovirology HTLV and Related Viruses
Place of Presentation
Montreal, Canada
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[Presentation] Diverse ways of modulating Polycomb group function and host epigenome in adult T cell leukemia2013
Author(s)
Yamagishi M, Fujikawa D, Kurokawa N, Soejima A, Nakagawa S, Nakano K, Utsunomiya A, Yamaguchi K, Uchimaru K, Watanabe T
Organizer
第75回日本血液学会学術集会
Place of Presentation
ロイトン札幌, 札幌
Related Report
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[Presentation] The CD7 vs CADM1 plot in FACS is useful for selecion of advanced HTLV-1 carriers2013
Author(s)
Kobayashi S, Watanabe E, Ishigaki T, Ohno N, Yuji K, Nakano K, Yamochi T, Watanabe T, Watanabe N, Tojo A, Uchimaru K
Organizer
第75回日本血液学会学術集会
Place of Presentation
ロイトン札幌, 札幌
Related Report
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[Presentation] Whole exome analysis reveals mutations of TET2 in adult T-cell leukemia/lymphoma2013
Author(s)
Nagata Y, Sato-Otsubo A, Okuno Y, Shiraishi Y, Chiba K, Tanaka H, Kon A, Yoshida K, Sanada M, Ishiyama K, Miyawaki S, Kitanaka A, Shimoda K, Miyano S, Watanabe T, Ogawa S
Organizer
18th Congress of EHA
Place of Presentation
Stockholm, Sweden
Related Report
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[Presentation] Molecular hallmarks of adult T cell leukemia: miRNA, pigenetics, and emerging signaling abnormalities2013
Author(s)
Yamagishi M, Fujikawa D, Kurokawa N, Soejima A, Takahashi R, Sakai N, Nakagawa S, Nakano K, Kobayashi S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
Organizer
16th International Conference on Human Retrovirology HTLV and Related Viruses
Place of Presentation
Montreal, Canada
Related Report
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[Presentation] The CD7 vs CADM1 plot in FACS is useful for selecion of advanced HTLV-1 carriers2013
Author(s)
Kobayashi S, Watanabe E, Ishigaki T, Ohno N, Yuji K, Nakano K, Yamochi T, Watanabe T, Watanabe N, Tojo A, Uchimaru K
Organizer
第75回日本血液学会学術集会
Place of Presentation
ロイトン札幌
Related Report
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[Presentation] Genetic and Epigenetic Loss of miR-31 Activates NIK-dependent NF-κ B Pathway in Adult T-cell Leukemia2011
Author(s)
Yamagisi M, Nakano K, Yamochi T, Miyake A, Kagami Y, Tsutsumi A, Otsubo A, Ogawa S, Utsunomiya A, Yamaguchi K, Uchimaru K, Watanabe T
Organizer
The 15th International Conference on Human Retrovirology : HTLV and Related Viruses
Place of Presentation
Lueven, Belgium
Related Report
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[Presentation] Genetic and Epigenetic Loss of miR-31 Activates NIK-dependent NF-κB Pathway in Adult T-cell Leukemia2011
Author(s)
Yamagisi M, Nakano K, Yamochi T, Miyake A, Kagami Y, Tsutsumi A, Otsubo A, Ogawa S, Utsunomiya A, Yamaguchi K, Uchimaru K, Watanabe T
Organizer
The 15^<th> International Conference on Huma Retrovirology : HTLV and Related Viruses
Place of Presentation
Lueven, Belgium
Related Report
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[Presentation] Genetic and Epigenetic Loss of miR-31 Activates NIK-dependent NF-κB Pathway in Adult T-cell Leukemia2011
Author(s)
Yamagishi M, Nakano K, Yamochi T, Miyake A, Kagami Y, Tsutsumi A, Matsubara A, Ogawa S, Utsunomiya A, Yamaguchi K, Uchimaru K, Watanabe T
Organizer
The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
Place of Presentation
Yayoi Auditorium, The University of Tokyo, Tokyo
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