2013 Fiscal Year Final Research Report
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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| 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 |
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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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Research Products
(34 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)
Peer Reviewed
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[Journal Article] Adult T-cell leukemia cells are characterized by abnormalities of Helios expression that promotes T-cell growth2013
Author(s)
Asanuma S, Yamagishi M, Kawanami K, Nakano K, Sato-Otsubo A, Muto S, Sanada M, Yamochi T, Kobayashi S, Utsunomiya A, Iwanaga M, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
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Journal Title
Cancer Sci
Volume: 104(8)
Pages: 1097-1106
DOI
Peer Reviewed
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[Journal Article] Polycomb-mediated loss of miR-31 activates NIK-dependent NF-kB pathway in adult T-cell leukemia and other cancers2012
Author(s)
Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y, Tsutsumi A, Matsuda Y, Sato-Otsubo A, Muto S, Utsunomiya A, Yamaguchi K, Uchimaru K, Ogawa S, Watanabe T
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Journal Title
Cancer Cell
Volume: 21(1)
Pages: 121-135
DOI
Peer Reviewed
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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
Year and Date
20131011-13
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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
Year and Date
20131011-13
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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
Year and Date
20130626-30
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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
Year and Date
20110605-08
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