Clonal evolution of tumor-infiltrating cells in T-cell lymphomas

• Project/Area Number: 16K15497
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: Sakata-Yanagimoto Mamiko 筑波大学, 医学医療系, 准教授 (80451805)
• Co-Investigator(Renkei-kenkyūsha): CHIBA Shigeru 筑波大学, 医学医療系, 教授 (60212049)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: T細胞リンパ腫 / TET2 / RHOA / クローン進化 / 支持環境細胞 / 前がん細胞

Outline of Final Research Achievements

We previously identified that multistep acquisition of mutations are the important mechanisms for T-cell lymphomas. Mutations in TET2 gene, encoding an epigenetic modifier are the key for evolution of premalignant cells. The RHOA mutations are the driver for development of T-lineage tumor cells from premalignant cells. In this study, we established a mouse model showing that the tumors are supported by tumor-infiltrating cells evolved from premalignant cells.

Research Products

• [Journal Article] Progression to polythythemia vera from familial thrombocytosis with germline JAK2 R867Q mutation (2018)
  • Author(s): Maie Koichiro、Yokoyama Yasuhisa、Yano Yoko、Kato Takayasu、Nannya Yasuhito、Ogawa Seishi、Noguchi Masayuki、Sakata-Yanagimoto Mamiko、Chiba Shigeru
  • Journal Title: Annals of Hematology Volume: 97 Issue: 4 Pages: 737-739
  • DOI: 10.1007/s00277-017-3209-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Liquid biopsy for the identification of intravascular large B-cell lymphoma (2018)
  • Author(s): Suehara Yasuhito、Sakata-Yanagimoto Mamiko、et al
  • Journal Title: Hematologica Volume: in press Issue: 6 Pages: e241-e244
  • DOI: 10.3324/haematol.2017.178830
  • Peer Reviewed / Open Access
• [Journal Article] Droplet digital PCR assay and PNA-LNA clamp method for RHOA mutation detection in angioimmunoblastic T-cell lymphoma (2018)
  • Author(s): Tanzima Nuhat S, Sakata-Yanagimoto M, Komori D, Hattori K, Suehara Y, Fukumoto K, Fujisawa M, Kusakabe M, Matsue K, Wakamatsu H, Shimadzu M, Chiba S
  • Journal Title: Cancer Sci Volume: - Issue: 5 Pages: 1682-1689
  • DOI: 10.1111/cas.13557
  • Peer Reviewed / Open Access
• [Journal Article] Detection of the circulating tumor DNAs in angioimmunoblastic T- cell lymphoma (2017)
  • Author(s): Sakata-Yanagimoto Mamiko、Nakamoto-Matsubara Rie、Komori Daisuke、Nguyen Tran B.、Hattori Keiichiro、Nanmoku Toru、Kato Takayasu、Kurita Naoki、Yokoyama Yasuhisa、Obara Naoshi、Hasegawa Yuichi、Shinagawa Atsushi、Chiba Shigeru
  • Journal Title: Annals of hematology Volume: 96 Issue: 9 Pages: 1471-1475
  • DOI: 10.1007/s00277-017-3038-2
  • Peer Reviewed / Open Access
• [Journal Article] A single institutional retrospective evaluation for younger patients with primary central nervous lymphomas on a modified R-MPV regimen followed by radiotherapy and high dose cytarabine (2017)
  • Author(s): Hattori Keiichiro、Sakata-Yanagimoto Mamiko、Okoshi Yasushi、Kato Takayasu、Kurita Naoki、Yokoyama Yasuhisa、Obara Naoshi、Takano Shingo、Ishikawa Eiichi、Yamamoto Tetsuya、Matsumura Akira、Hasegawa Yuichi、Chiba Shigeru
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 57 Issue: 2 Pages: 41-46
  • DOI: 10.3960/jslrt.17012
  • NAID: 130006854539
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma (2017)
  • Author(s): Fujisawa M., Sakata-Yanagimoto M., Nishizawa S., Komori D., Gershon P., Kiryu M., Tanzima S., Fukumoto K., Enami T., Muratani M., Yoshida K., Ogawa S., Matsue K., Nakamura N., Takeuchi K., Izutsu K., Fujimoto K., Teshima T., Miyoshi H., Gaulard P., Ohshima K., Chiba S.
  • Journal Title: Leukemia Volume: 32 Issue: 3 Pages: 694-702
  • DOI: 10.1038/leu.2017.273
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma (2017)
  • Author(s): Fukumoto K、Nguyen TB、Chiba S、Sakata-Yanagimoto M
  • Journal Title: Cancer Sci Volume: 109 Issue: 3 Pages: 490-496
  • DOI: 10.1111/cas.13393
  • NAID: 120007134344
  • Peer Reviewed / Open Access
• [Journal Article] Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma (2017)
  • Author(s): Hattori Keiichiro、Sakata-Yanagimoto Mamiko、Suehara Yasuhito、Yokoyama Yasuhisa、Kato Takayasu、Kurita Naoki、Nishikii Hidekazu、Obara Naoshi、Takano Shingo、Ishikawa Eiichi、Matsumura Akira、Hasegawa Yuichi、Chiba Shigeru
  • Journal Title: Cancer science Volume: 109 Issue: 1 Pages: 225-230
  • DOI: 10.1111/cas.13450
  • NAID: 120007134545
  • Peer Reviewed / Open Access
• [Journal Article] Recent Progress in the Understanding of Angioimmunoblastic T-cell Lymphoma (2017)
  • Author(s): Fujisawa M, Chiba S, Sakata-Yanagimoto M
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 57 Issue: 3 Pages: 109-119
  • DOI: 10.3960/jslrt.17019
  • NAID: 130006286291
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] BCL6 locus is hypermethylated in angioimmunoblastic T-cell lymphoma. (2017)
  • Author(s): Nishizawa S, Sakata-Yanagimoto M, Hattori K, Muto H, Nguyen T, Izutsu K, Yoshida K, Ogawa S, Nakamura N, Chiba S.
  • Journal Title: Int J Hematol. Volume: - Issue: 4 Pages: 465-469
  • DOI: 10.1007/s12185-016-2159-z
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of cell-type-specific mutations in nodal T-cell lymphomas. (2017)
  • Author(s): Nguyen TB, Sakata-Yanagimoto M, Asabe Y, Matsubara D, Kano J, Yoshida K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Izutsu K, Nakamura N, Takeuchi K, Miyoshi H, Ohshima K, Minowa T, Ogawa S, Noguchi M, Chiba S.
  • Journal Title: Blood Cancer Journal Volume: 7 Issue: 1 Pages: e516-e516
  • DOI: 10.1038/bcj.2016.122
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathologic analysis of angioimmunoblastic T-cell lymphoma with or without RHOA G17V mutation using formalin-fixed paraffin-embedded sections. (2016)
  • Author(s): Nagao R, Kikuti YY, Carreras J, Kikuchi T, Miyaoka M, Matsushita H, Kojima M, Ando K, Sakata-Yanagimoto M, Chiba S, Nakamura N.
  • Journal Title: Am J Surg Pathol Volume: 40 Issue: 8 Pages: 1041-50
  • DOI: 10.1097/pas.0000000000000651
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] MYD88 (L265P) mutation is associated with an unfavourable outcome of primary central nervous system lymphoma. (2016)
  • Author(s): Hattori K, Sakata-Yanagimoto M, Okoshi Y, Goshima Y, Yanagimoto S, Nakamoto-Matsubara R, Sato T, Noguchi M, Takano S, Ishikawa E, Yamamoto T, Matsumura A, Chiba S.
  • Journal Title: Br J Haematol Volume: - Issue: 3 Pages: 492-494
  • DOI: 10.1111/bjh.14080
  • Peer Reviewed / Open Access
• [Presentation] A new understanding of angioimmunoblastic T-cell lymphoma by integrating its genomics and biology (2018)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: The 14th Japanese-Korean Lymphoreticular Workshop 2018
  • Int'l Joint Research / Invited
• [Presentation] The role of RHOA mutations in T-cell lymphomas (2018)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 10th Annual T-cell Lymphoma Forum 2018
  • Int'l Joint Research / Invited
• [Presentation] Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma (2017)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 14th International Conference on Malignant Lymphoma
  • Int'l Joint Research
• [Presentation] A novel function of the G17V RHOA mutant in angioimmunoblastic T- cell lymphoma (2017)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第76回日本癌学会学術総会
  • Invited
• [Presentation] Recurrent VAV1 Abnormalities in Angioimmunoblastic T Cell Lymphoma (2016)
  • Author(s): Daisuke Komori
  • Organizer: The American Society of Hematology 58th Annual Meeting and Exposition
  • Place of Presentation: San Diego Convention Center, San Diego, CA, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] 多段階的遺伝子変異獲得による血液がんの発症メカニズム (2016)
  • Author(s): 坂田（柳元）麻実子
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜, 横浜, 神奈川
  • Year and Date: 2016-11-30
  • Invited
• [Presentation] 血液がんの起源と進展のメカニズム (2016)
  • Author(s): 坂田（柳元）麻実子
  • 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, 神奈川
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] Combined loss of Tet2 and Tet3 induces AML sensitive to hypomethylating agents (2016)
  • Author(s): Koichiro Maie
  • 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, 神奈川
  • Year and Date: 2016-10-13
• [Presentation] MyD88 mutation as an unfavorable prognostic factor of primary central nervous system lymphoma (2016)
  • Author(s): 服部圭一朗
  • 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, 神奈川
  • Year and Date: 2016-10-13
• [Presentation] Integrity of TET dioxygenase activity determines leukemic transformation (2016)
  • Author(s): Koichiro Maie
  • Organizer: 第76回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜, 横浜, 神奈川
  • Year and Date: 2016-10-06
• [Presentation] TET2 mutations: a predisposing factor for myeloid and T-cell malignancies (2016)
  • Author(s): Mamiko Sakata-Yanagimoto
  • Organizer: 第76回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜, 横浜, 神奈川
  • Year and Date: 2016-10-06
  • Invited
• [Presentation] MyD88 (L265P) mutation is associated with an unfavorable outcome of primary central nervous system lymphoma (2016)
  • Author(s): Keiichiro Hattori
  • Organizer: 第76回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜, 横浜, 神奈川
  • Year and Date: 2016-10-06
• [Presentation] Unveiling the molecular pathogenesis of Angioimmunoblastic T-cell lymphoma using laser microdissection based sequencing (2016)
  • Author(s): Tran B. Nguyen
  • Organizer: 第56回 日本リンパ網内系学会総会
  • Place of Presentation: ホテル日航熊本, 熊本
  • Year and Date: 2016-09-01
• [Presentation] Combined Loss of Tet2/Tet3 Dioxygenases Induces Acute Myeloid Leukemia Sensitive to Hypomethylating Agents (2016)
  • Author(s): Koichiro Maie
  • Organizer: The 5th JCA-AACR Special Joint Conference
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Urayasu, Chiba
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Presentation] Understanding the Molecular Pathogenesis of Peripheral T-cell Lymphoma by Laser Microdissection-based Sequencing (2016)
  • Author(s): Tran B. Nguyen
  • Organizer: The 5th JCA-AACR Special Joint Conference
  • Place of Presentation: Tokyo Bay Maihama Hotel Club Resort, Urayasu, Chiba
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Presentation] Unveiling the Molecular Pathogenesis of Angioimmunoblastic T-cell Lymphoma Using Laser Microdissection Based Sequencing (2016)
  • Author(s): Tran B. Nguyen
  • Organizer: The 35th Sapporo International Cancer Symposium 2016 Cancer Epigenome: From discovery to translation
  • Place of Presentation: Royton Sapporo, Sapporo, Hokkaido
  • Year and Date: 2016-06-24
  • Int'l Joint Research
• [Presentation] Double inactivation of tet2 and tet3 induces hypomethylating agent-sensitive acute myeloid leukemia. (2016)
  • Author(s): Koichiro Maie
  • Organizer: 21th Congress of EHA 2016
  • Place of Presentation: Bella Center, Copenhagen, Denmark
  • Year and Date: 2016-06-09
  • Int'l Joint Research
• [Presentation] Double inactivation of Tet2 and Tet3 induces hypomethylating agent-sensitive acute myeloid leukemia (2016)
  • Author(s): Koichiro Maie
  • Organizer: The 14th Stem Cell Research Symposium 第14回 幹細胞シンポジウム
  • Place of Presentation: Awaji Yumebutai International Conference Center, Awaji, Hyogo
  • Year and Date: 2016-05-20
  • Int'l Joint Research