Clarifying the pathogenesis of ABC-DLBCL in a mouse model

• Project/Area Number: 15K09474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: Nishikori Momoko 京都大学, 医学研究科, 講師 (60378635)
• Co-Investigator(Renkei-kenkyūsha): IWAI Kazuhiro 京都大学, 大学院医学研究科 細胞機能制御学講座, 教授 (60252459)
• Research Collaborator: JO Tomoyasu 京都大学, 大学院医学研究科血液・腫瘍内科学 ; ARIMA Hiroshi 京都大学, 大学院医学研究科血液・腫瘍内科学
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 悪性リンパ腫 / マウスモデル / Ｂ細胞リンパ腫 / MyD88 / HOIP / NF-kappaB

Outline of Final Research Achievements

To clarify the pathogenesis of ABC－type diffuse large B-cell lymphoma (DLBCL), we generated a mouse lymphoma model by crossing gene-engeneered mice carrying HOIP and mutant MyD88 transgenes. We have found how these genes cooperate with each other during lymphomagenesis.

Research Products

• [Journal Article] Prognostic impact of activation-induced cytidine deaminase expression for patients with diffuse large B-cell lymphoma (2018)
  • Author(s): Arima H、Fujimoto M、Nishikori M、Kitano T、Kishimoto W、Hishizawa M、Kondo T、Yamashita K、Hirata M、Haga Hironori、Takaori-Kondo A.
  • Journal Title: Leukemia & Lymphoma Volume: 印刷中 Issue: 9 Pages: 2085-2095
  • DOI: 10.1080/10428194.2017.1410884
  • Peer Reviewed / Open Access
• [Journal Article] PD-1 blockade therapy in lymphoid malignancies (2017)
  • Author(s): Nishikori M, Takaori-Kondo A.
  • Journal Title: Rinsho Ketsueki Volume: 58 Issue: 10 Pages: 2043-2049
  • DOI: 10.11406/rinketsu.58.2043
  • NAID: 130006132715
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed / Open Access
• [Journal Article] Outcome of allogeneic hematopoietic stem cell transplantation in cases of mature T/NK-cell neoplasms: a single-center retrospective analysis. (2017)
  • Author(s): Yamazaki H, Aoki K, Kondo T, Nishikori M, Kitano T, Hishizawa M, Yamashita K, Takaori-Kondo A.
  • Journal Title: Annals of Hematology Volume: 96 Issue: 2 Pages: 323-326
  • DOI: 10.1007/s00277-016-2858-9
  • Peer Reviewed / Open Access
• [Journal Article] Expression of Tim-1 in primary CNS lymphoma. (2016)
  • Author(s): Kishimoto W, Nishikori M, Arima H, Miyoshi H, Sasaki Y, Kitawaki T, Shirakawa K, Kato T, Imaizumi Y, Ishikawa T, Ohno H, Haga H, Oshima K, Takaori-Kondo A.
  • Journal Title: Cancer Medicine Volume: 5 Issue: 11 Pages: 3235-45
  • DOI: 10.1002/cam4.930
  • NAID: 120005867107
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Efficacy and safety of ibrutinib in Japanese patients with relapsed or refractory mantle cell lymphoma. (2016)
  • Author(s): Maruyama D, Nagai H, Fukuhara N, Kitano T, Ishikawa T, Shibayama H, Choi I, Hatake K, Uchida T, Nishikori M, Kinoshita T, Matsuno Y, Nishikawa T, Takahara S, Tobinai K.
  • Journal Title: Cancer Sci. Volume: 107 Issue: 12 Pages: 1785-1790
  • DOI: 10.1111/cas.13076
  • NAID: 120005997907
  • Peer Reviewed / Open Access
• [Journal Article] Diminished CD2 expression in T cells permits tumor immune escacpe. (2016)
  • Author(s): Nishikori M, Kitawaki T, Tashima M, Shimazu Y, Mori M, Hishizawa M, Kondo T, Ohmori K, Takaori-Kondo A.
  • Journal Title: Journal of Clinical and Cellular Immunology Volume: 7 Issue: 02 Pages: 406-406
  • DOI: 10.4172/2155-9899.1000406
  • Peer Reviewed / Open Access
• [Journal Article] A case of neurolymphomatosis caused by follicular lymphoma successfully treated with bendamustine. (2016)
  • Author(s): Umeda M, Kondo T, Nishikori M, Kitano T, Hishizawa M, Kadowaki N, Takaori-Kondo A.
  • Journal Title: Clinical Case Reports Volume: 4 Issue: 1 Pages: 23-25
  • DOI: 10.1002/ccr3.436
  • NAID: 120005838166
  • Peer Reviewed / Open Access
• [Journal Article] Increased number of peripheral CD8+ T cells but not eosinophils is associated with late-onset skin reactions caused by bendamustine. (2015)
  • Author(s): Nishikori M, Kitano T, Kobayashi M, Hishizawa M, Kitawaki T, Kondo T, Yamashita K, Kawabata H, Kadowaki N, Takei Y, Haga H, Takaori-Kondo A.
  • Journal Title: Int J Hematol. Volume: 未定 Issue: 1 Pages: 53-58
  • DOI: 10.1007/s12185-015-1791-3
  • NAID: 120005674658
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] STX11 functions as a novel tumor suppressor gene in peripheral T-cell lymphomas. (2015)
  • Author(s): Yoshida N, Tsuzuki S, Karube K, Takahara T, Suguro M, Miyoshi H, Nishikori M, Shimoyama M, Tsukasaki K, Ohshima K, Seto M.
  • Journal Title: Cancer Science Volume: 106 Issue: 10 Pages: 1455-62
  • DOI: 10.1111/cas.12742
  • NAID: 120005767013
  • Peer Reviewed / Open Access
• [Presentation] 極めて長期の寛解期間後に再発した悪性リンパ腫の2症例 (2017)
  • Author(s): 大塚泰幸、錦織桃子、岡知美、北野俊行、高折晃史
  • Organizer: 第57回日本リンパ網内系学会総会
• [Presentation] Immunomodulatory function of Notch1-activated B cells and its implications in tumor immune escape of B-cell malignancies. (2017)
  • Author(s): Arima H, Nishikori M, Otsuka Y, Kishimoto W, Izumi K, Takaori-Kondo A.
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] A retrospective analysis of outcomes of primary central nervous system lymphoma patients. (2017)
  • Author(s): Otsuka Y, Nishikori M, Hishizawa M, Kitano T, Kitawaki T, Kondo T, Yamashita K, Takaori-Kondo A.
  • Organizer: 第79回 日本血液学会学術集会
• [Presentation] Immunomodulatory function of Notch1-activated B cells and its implication in the pathogenesis of B-cell malignancies. (2017)
  • Author(s): Arima H, Nishikori M, Otsuka Y, Kishimoto W, Izumi K, Takaori-Kondo A.
  • Organizer: 第79回 日本血液学会学術集会
• [Presentation] リンパ腫診療における免疫チェックポイント阻害剤の役割 (2017)
  • Author(s): 錦織桃子、髙折晃史．
  • Organizer: 第57回日本リンパ網内系学会総会 シンポジウム5
  • Invited
• [Presentation] リンパ系腫瘍に対するPD-1阻害治療 (2017)
  • Author(s): 錦織桃子
  • Organizer: 第79回 日本血液学会学術集会
  • Invited
• [Presentation] Notch-1-activated B cells have an immunomodulatory function enhancing Th2 and Treg immune response via IL-33-ST2 pathway. (2016)
  • Author(s): Arima H, Nishikori M, Otsuka Y, Izumi K, Kishimoto W, Takaori-Kondo A.
  • Organizer: 第58回 米国血液学会総会
  • Place of Presentation: San Diego
  • Year and Date: 2016-12-04
  • Int'l Joint Research
• [Presentation] Prognostic significance of early progression after initial chemotherapy varies with age in follicular lymphoma patients. (2016)
  • Author(s): Kishimoto W, Tashima M, Nishikori M, Arima H, Hishizawa M, Kitano T, Takaori-Kondo A.
  • Organizer: 第78回 日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-14
• [Presentation] Constitutive activation of Notch1 in mature B cells causes cellular immunodeficiency in mice. (2016)
  • Author(s): Arima H, Nishikori M, Otsuka Y, Kishimoto W, Shirakawa K, Takaori-Kondo A.
  • Organizer: 第75回 日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-07
• [Presentation] PD-1 blockade for the treatment of lymphoid malignancies. (2016)
  • Author(s): Nishikori M, Kitawaki T, Takaori-Kondo A.
  • Organizer: 第７回 日本血液学会国際シンポジウム
  • Place of Presentation: 淡路
  • Year and Date: 2016-05-13
  • Int'l Joint Research / Invited
• [Presentation] 悪性リンパ腫における免疫チェックポイント阻害剤の基礎と臨床 (2015)
  • Author(s): 錦織桃子、高折晃史
  • Organizer: 日本リンパ網内系学会総会 （シンポジウム２）
  • Place of Presentation: 岡山
  • Year and Date: 2015-07-10
  • Invited