The elucidation study about an onset mechanism of the EB virus-related PTLD

• Project/Area Number: 15K15116
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Imadome Ken-Ichi 国立研究開発法人国立成育医療研究センター, 高度感染症診断部, 部長 (70392488)
• Research Collaborator: KAWANO Fuyuko 国立成育医療研究センター, 高度先進医療研究室, 研究員 (80790469)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: EBウイルス / 肝移植 / PTLD / 生体イメージング / リンパ増殖症 / EBV / EBV-PTLD / 移植医療後のリンパ増殖症

Outline of Final Research Achievements

We aimed at the establishment of prevention and the therapy of lymphatic hyperplasia (PTLD:post-transplant lymphoproliferative disorder) after EB virus (EBV)-related transplant.After at first having multiplied in liver, the infected cells which shifted with a graft were supplied in peripheral blood, and it was shown that we made niche to the other organ and lymph nodes and were connected for the PTLD onset.Also, increase (more than 3 times) of the PTLD incidence was shown by a person or a mouse under the immunosuppressive drug administration.
This study suggested that choice of the optimal quantity of the quantity of immunosuppressive drug was important.

Research Products

• [Journal Article] Clinically Mild Encephalitis/Encephalopathy With a Reversible Splenial Lesion Accompanied by Epstein-Barr Virus Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature. (2017)
  • Author(s): Yamaguchi H., Ishida T., Yokoi T., Tanaka T., Maruyama A., Nagase H., Hasegawa D., Imadome K., Takeda H., Kosaka Y., Uetani Y.
  • Journal Title: J Pediatr Hematol Oncol. Volume: 39(2) Issue: 2 Pages: 92-96
  • DOI: 10.1097/mph.0000000000000708
  • Peer Reviewed / Open Access
• [Journal Article] EBV induces persistent NF-κB activation and contributes to survival of EBV-positive neoplasmtic T- or NK-cells. (2017)
  • Author(s): Imadome K*., Takada H*. , Shibayama H., Yoshimori M., Wang L., Saitoh Y., Uota S., Yamaoka S., Koyama T., Shimizu N., Yamamoto K., Fujiwara S., Miura O., Arai A.
  • Journal Title: PLoS One. Volume: 12(3) Issue: 3 Pages: e0174136-e0174136
  • DOI: 10.1371/journal.pone.0174136
  • Peer Reviewed / Open Access
• [Journal Article] Generation and analysis of humanized mouse model of EBV infection. (2017)
  • Author(s): Imadome K., Fujiwara S.
  • Journal Title: Methods Mol Biol. Volume: 1532 Pages: 241-254
  • Peer Reviewed
• [Journal Article] Transmission of chromosomally integrated humanherpesvisus 6 via cord blood transplantation. (2017)
  • Author(s): Yamada Y., Osumi T., Imadome K., Takahashi E., Ohye T., Yoshikawa T., Tomizawa D., Kato M., Matsumoto K.
  • Journal Title: Transpl Infect Dis. Volume: 19(1) Issue: 1 Pages: 1-4
  • DOI: 10.1111/tid.12636
  • Peer Reviewed
• [Journal Article] Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation (2016)
  • Author(s): Matsui S, Takeda Y, Isshiki Y, Yamazaki A, Nakao S, Takaishi K, Nagao Y, Hasegawa N, Togasaki E., Shimizu R., Kawajiri C., Sakai S., Mimura N., Takeuchi M., Ohwada C., Sakaida E., Iseki T., Imadome K., Nakaseko C.
  • Journal Title: Rinsho Ketsueki Volume: 57 Issue: 5 Pages: 624-629
  • DOI: 10.11406/rinketsu.57.624
  • NAID: 130005155378
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Hematopoietic stem cell transplantation for adults with EBV-positive T- or NK- cell lymphoproliferative disorders: efficacy and predictive markers. (2016)
  • Author(s): Arai A., Sakashita C., Hirose C., Imadome K., Yamamoto M., Jinta M., Fujiwara S., Tomita M., Shimizu N., Morio T., Miura O.
  • Journal Title: Bone Marrow Transplant. Volume: 22 Issue: 6 Pages: 879-82
  • DOI: 10.1038/bmt.2016.3
  • Peer Reviewed / Open Access
• [Journal Article] Epstein-Barr Virus-positive T-cell Lymphoproliferative Disease Following Umbilical Cord Blood Transplantation for Acute Myeloid Leukemia (2016)
  • Author(s): Yui S., Yamaguchi H., Imadome K., Arai A., Takahashi M., Ohashi R., Asayama T., Kondo A., Moriya K., Nakayama K., Dan K., Shimizu S., Inokuchi K.
  • Journal Title: Journal of Nippon Medical School Volume: 83 Issue: 1 Pages: 35-42
  • DOI: 10.1272/jnms.83.35
  • NAID: 130005132782
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed / Open Access
• [Journal Article] P-glycoprotin is expressed and causes resistance to chemotherapy in EBV-positive T-cell lymphoproliferative diseases. (2015)
  • Author(s): Yoshimori M., Takeda H., Imadome K., Kurata M., Yamamoto K., Koyama T., Shimizu N., Fujiwara S., Miura O., Arai A
  • Journal Title: Cancer Med. Volume: 4 Pages: 1494-1504
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Immune-mediated Neuropathy with Epstein-Barr virus-positive T-cell Lymphoproliferative Disease (2015)
  • Author(s): Matsuda G., Imadome K., Kawano F., Mochizuki M., Ochiai N., Morio T., Shimizu N., Fujiwara S.
  • Journal Title: Internal Medicine Volume: 54 Issue: 1 Pages: 69-73
  • DOI: 10.2169/internalmedicine.54.3173
  • NAID: 130004902994
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Evaluation of the Immune Function Assay in Pediatric Living Donor Liver Transplantation (2015)
  • Author(s): Akinari Fukuda, Ken-Ichi Imadome, Seisuke Sakamoto, Takanobu Shigeta, Hajime Uchida, Masatoshi Matsunami, Kengo Sasaki, Hiroyuki Kanazawa, Fuyuko Kawano, Atsuko Nakazawa, Shigeyoshi Fujiwara, and Mureo Kasahara
  • Journal Title: Pediatric Transplantation Volume: 19(2) Issue: 2 Pages: 144-152
  • DOI: 10.1111/petr.12402
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Modeling EBV infection and pathogenesis in new-generation humanized mice (2015)
  • Author(s): Fujiwara S, Imadome K, and Takei M
  • Journal Title: Exp Mol Med Volume: 47 Issue: 1 Pages: e135-e135
  • DOI: 10.1038/emm.2014.88
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] In vitro and in vivo effects of bortezomib on EBV-T/NK-LPDs (2016)
  • Author(s): Haruna Shibayama, Ken-Ichi Imadome, Chizuko Sakashita, Ken Watanabe, Fuyuko Kawano, Norio Shimizu, Takatoshi Koyama, Shigeyoshi Fujiwara, Osamu Miura, Ayako Arai
  • 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] 移植治療後の日和見感染症関連ウイルス疾患の病態把握と治療戦略 (2016)
  • Author(s): 今留謙一
  • Organizer: 第52回日本移植学会
  • Place of Presentation: 東京
  • Year and Date: 2016-09-30
  • Invited
• [Presentation] EBウイルスEBNA3C の新たな局在化シグナル (2016)
  • Author(s): 松田剛、今留謙一
  • Organizer: 第30回ヘルペスウイルス研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-16
• [Presentation] 難治性EBウイルス関連T/NKリンパ増殖性疾患モデルマウスを用いた治療薬の評価研究 (2016)
  • Author(s): 川野布由子、新井文子、伊藤守、清水則夫、松田剛、藤原成悦、今留謙一
  • Organizer: 第30回ヘルペスウイルス研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-16
• [Presentation] EBV関連難治性疾患における病態予測因子の探索と感染細胞産生sFasの役割について (2016)
  • Author(s): 古田頌子、川野布由子、渡邊健、松岡浩、清水則夫、松田剛、今留謙一
  • Organizer: 第30回ヘルペスウイルス研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-06-16
• [Presentation] EBウイルスゲノムコピー数の簡単迅速定量系の構築 (2016)
  • Author(s): 外丸靖浩、渡邊健、清水則夫、今留謙一
  • Organizer: 第13回EBウイルス研究会
  • Place of Presentation: 東京
• [Presentation] EBV関連T/NK細胞リンパ増殖症の病態把握と診断および治療戦略 (2016)
  • Author(s): 今留謙一
  • Organizer: 第10回北海道小児先進医療研究会
  • Place of Presentation: 旭川
  • Invited
• [Presentation] EBV関連T/NK細胞リンパ増殖症の診断と治療および最新の基礎研究の現状 (2016)
  • Author(s): 今留謙一
  • Organizer: EBウイルス感染と血液疾患研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] An evaluation of a novel curative medicine S-FMAU, utilizing intractable EBV associated with T/NK lymphoproliferative disorder model mouse. (2015)
  • Author(s): 川野布由子、児玉栄一、新井文子、清水則夫、伊藤守、藤原成悦、今留謙一
  • Organizer: 第63回日本ウイルス学会
  • Place of Presentation: 長崎
  • Year and Date: 2015-11-22
• [Presentation] Identification of new nuclear localization signal in Epstein-Barr Virus EBNA3C (2015)
  • Author(s): 松田剛、今留謙一
  • Organizer: 第63回日本ウイルス学会
  • Place of Presentation: 長崎
  • Year and Date: 2015-11-22
• [Presentation] Role of tumor-derived secretary small RNAs in macrophages in EBV positive lymphoma formation (2015)
  • Author(s): Naysuko Yamakawa, Ken-Ichi Imadome, Ai Kotani
  • Organizer: 第44回日本免疫学会
  • Place of Presentation: 長崎
  • Year and Date: 2015-11-18
• [Presentation] EBV関連リンパ増殖性疾患モデルマウスでの腎臓の腫瘍化に関与するEBV遺伝子発現解析 (2015)
  • Author(s): 松田剛、川野布由子、藤原成悦、今留謙一
  • Organizer: 第29回ヘルペスウイルス研究会
  • Place of Presentation: 長崎
  • Year and Date: 2015-06-04
• [Presentation] Role of tumor-derived secretary small RNAs in macrophages in EBV positive lymphoma formation (2015)
  • Author(s): Natsuko Yamakawa, Ken-Ichi Imadome, Takashi Yahata, Ai Kotani
  • Organizer: The 2015 Keystone symposia on Molecular & Cellular Biology
  • Place of Presentation: Keystone
  • Year and Date: 2015-05-17
  • Int'l Joint Research
• [Book] EBV関連リンパ増殖性疾患：概念と病態解析研究の進歩 (2015)
  • Author(s): 今留謙一
  • Total Pages: 10
  • Publisher: 血液内科