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Investigation of mechanisms underlying the development of lymphoma and myeloma using a high-throughput mouse model system

Research Project

Project/Area Number 15K09492
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionAichi Medical University (2016-2017)
Aichi Cancer Center Research Institute (2015)

Principal Investigator

Tsuzuki Shinobu  愛知医科大学, 医学部, 教授 (00342965)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥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 / レトロウイルス / 遺伝子導入 / 遺伝子変異 / CARD11 / BCL6
Outline of Final Research Achievements

We have investigated causative roles of given genes or mutated genes in the development of malignant lymphoma and multiple myeloma using our high-throughput mouse model system, in which germinal center B cells (normal counterparts of many lymphomas) were induced in vitro, infected with retroviruses for gene of interest, and transplanted into mice. Results showed that a combination of CARD11 mutant and BCL6 or a combination of Myc and Bcl2 was sufficient for the development of lymphoma. Our models may provide a platform for the development of therapy of these lymphomas known as being associated with poor clinical outcome. Although we were unable to develop a mouse myeloma model within the assigned period of time, we have developed a Cre-LoxP-mediated gene expression system employing retrovirus vector, and thus will make an effort to accomplish the aims.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Synergistic activity of Card11 mutant and Bcl6 in the development of diffuse large B-cell lymphoma in a mouse model.2016

    • Author(s)
      Taishi Takahara,Keitaro Matuo,Masao Seto,Shigeo Nakamura,Shinobu Tsuzuki
    • Journal Title

      Cancer Science

      Volume: 107 Issue: 11 Pages: 1572-1589

    • DOI

      10.1111/cas.13057

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] BLNK is a selective target of repression by PAX5-PML in the differentiation block that leads to the development of acute lymphoblastic leukemia.2016

    • Author(s)
      Imoto N, Hayakawa F, Kurahashi S, Morishita T, Kojima Y, Yasuda T, Sugimoto K, Tsuzuki S, Naoe T, Kiyoi H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 9 Pages: 4723-31

    • DOI

      10.1074/jbc.m115.637835

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / 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

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The rs3779620 in the PBK gene is closely associated with myeloma cell growth2017

    • Author(s)
      Ota Akinobu, Karnan Sivasundaram, Md Wahiduzzaman, Mizuno Shohei, Uchino Kaori, Kanasugi Jo, Horio Tomohiro, Murakami Satsuki, Suzuki Susumu, Tsuzuki Shinobu, Konishi Hiroyuki, Ueda Ryuzo, Hosokawa Yoshitaka, Takami Akiyoshi
    • Organizer
      第79会 日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] High expression of MEF2D-fusion protein by escaping from the regulation by microRNA2017

    • Author(s)
      Hirano Daiki, Hayakawa Fumihiko, Yasuda Takahiko, Yamamoto Hideyuki, Kojima Yuki, Morishita Takanobu, Imoto Naoto, Tsuzuki Shinobu, Mano Hiroyuki, Naoe Tomoki, Kiyoi Hitoshi
    • Organizer
      第79会 日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Synergistic activity of Card11 mutant and Bcl6 genes in the development of diffuse large B cell lymphoma in a mouse model2016

    • Author(s)
      高原大志 中村栄男 松尾恵太朗 瀬戸正夫 都築忍
    • Organizer
      Korean-Japanese Lymphoreticular Workshop 2016
    • Place of Presentation
      MAYFIELD Hotel(韓国 ソウル市)
    • Year and Date
      2016-01-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] マウスモデルを用いたDiffuse large B cell lymphoma(DLBCL)関連遺伝子の機能解析2015

    • Author(s)
      高原大志 都築忍
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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