• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the high-grade pathogenesis of universal mature B cell tumor model by using comprehensive gene editing

Research Project

Project/Area Number 21K16274
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Mizutani Shinsuke  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40883088)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsB細胞性リンパ腫 / 多発性骨髄腫 / PDPK1 / RSK2
Outline of Research at the Start

B細胞性リンパ腫(B cell lymphoma; BCL)、多発性骨髄腫(Multiple myeloma; MM)は、高頻度造血器腫瘍であるが、難治症例の克服が、いまだ重要課題として残されている。本研究ではヒト正常B細胞由来不死化細胞株にPDPK1-RSK2シグナル恒常的活性化を誘導した「BCL疾患横断的・普遍的モデル細胞」を作成し、高度造腫瘍性、細胞死刺激抵抗性獲得、染色体・遺伝子不安定性、抗腫瘍細胞免疫回避機構を誘導する分子異常の同定を目指す。さらに患者細胞の解析によって、その臨床的意義について明らかにし、高度難治BCL、MMの克服戦略開発のための基盤知見を確立する

Outline of Final Research Achievements

B cell lymphoma (BCL) and multiple myeloma (MM) are highly prevalent hematopoietic tumors, and overcoming refractory cases remains an important challenge. In this study, we generated "BCL disease-cross-sectional and universal model cells" by inducing PDPK1-RSK2 signaling homeostatic activation in an immortalized human normal B cell-derived cell line, and performed a comprehensive screening of human whole genome CRISPR/Cas9 gene knockout against these cells to identify cells with high tumorigenicity, resistance to cell death stimulation, chromosomal and genetic instability We are in the process of identifying molecular abnormalities that induce high tumorigenicity, resistance to cell death stimulation, chromosomal and genetic instability, and anti-tumor cell immune evasion mechanisms.

Academic Significance and Societal Importance of the Research Achievements

本研究でBCL、MMにおけるPDPK1-RSK2シグナルの恒常的活性化の病型横断的・普遍的な病態形成する「がん抑制遺伝子、がん遺伝子」が同定できれば、染色体・遺伝子不安定性獲得によるクローン性進化、骨髄由来抑制系細胞誘導機序等の解明に繋がり、一部の症例に認める高度治療抵抗性獲得病態を司る付加的分子異常の解明と克服に大きな一歩となるだけでなく、他のがん種に関する応用研究も期待できる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (9 results)

All 2023 2022 2021

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Deletion of the transcriptional regulator TFAP4 accelerates c-MYC-driven lymphomagenesis2023

    • Author(s)
      Potts Margaret A.、Mizutani Shinsuke、Garnham Alexandra L.、Li Wai Suen Connie S. N.、Kueh Andrew J.、Tai Lin、Pal Martin、Strasser Andreas、Herold Marco J.
    • Journal Title

      Cell Death & Differentiation

      Volume: - Issue: 6 Pages: 1447-1456

    • DOI

      10.1038/s41418-023-01145-w

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Imaging flow cytometry-based multiplex FISH for three IGH translocations in multiple myeloma2023

    • Author(s)
      Tsukamoto Taku、Kinoshita Masaki、Yamada Kazuhiro、Ito Hodaka、Yamaguchi Toshikazu、Chinen Yoshiaki、Mizutani Shinsuke、Fujino Takahiro、Kobayashi Tsutomu、Shimura Yuji、Inazawa Johji、Kuroda Junya
    • Journal Title

      Journal of Human Genetics

      Volume: - Issue: 7 Pages: 507-514

    • DOI

      10.1038/s10038-023-01136-2

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Treatment with Anti-CD20 Monoclonal Antibody on the Production of Neutralizing Antibody Against Anti?SARS-CoV-2 Vaccination in Mature B-Cell Neoplasms2023

    • Author(s)
      Onishi Akio、Matsumura-Kimoto Yayoi、Mizutani Shinsuke、Tsukamoto Taku、Fujino Takahiro、Miyashita Akihiro、Nishiyama Daichi、Shimura Kazuho、Kaneko Hiroto、Kawata Eri、Takahashi Ryoichi、Kobayashi Tsutomu、Uchiyama Hitoji、Uoshima Nobuhiko、Nukui Yoko、Shimura Yuji、Inaba Tohru、Kuroda Junya
    • Journal Title

      Infection and Drug Resistance

      Volume: Volume 16 Pages: 509-519

    • DOI

      10.2147/idr.s396271

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neurolymphomatosis of cranial nerves as the responsible lesions for the vocal cord paralysis and facial nerve palsy in a patient with diffuse large B-cell lymphoma2022

    • Author(s)
      Inoue Yu、Hirakawa Koichi、Hayata Hiroki、Nishiyama Daichi、Fujino Takahiro、Tsukamoto Taku、Mizutani Shinsuke、Shimura Yuji、Kuroda Junya
    • Journal Title

      Annals of Hematology

      Volume: 102 Issue: 2 Pages: 481-482

    • DOI

      10.1007/s00277-022-05038-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Watchful waiting is an acceptable treatment option for asymptomatic primary ocular adnexal mucosa‐associated lymphoid tissue lymphoma: A retrospective study2022

    • Author(s)
      Mizuhara Kentaro, Kobayashi Tsutomu, Nakao Mitsushige, Takahashi Ryoichi, Kaneko Hiroto, Shimura Kazuho, Hirakawa Koichi, Uoshima Nobuhiko, Wada Katsuya, Kawata Eri, Isa Reiko, Fujino Takahiro, Tsukamoto Taku, Mizutani Shinsuke, Shimura Yuji, Yoneda Akiko, Watanabe Akihide, Sotozono Chie, Kuroda Junya
    • Journal Title

      Cancer Medicine

      Volume: 12 Issue: 3 Pages: 3134-3144

    • DOI

      10.1002/cam4.5237

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Implication of the Effect of the Production of Neutralizing Antibodies Against SARS-Cov-2 for Chronic Immune Thrombocytopenia Flare-Up Associated with COVID-19 Infection: A Case Report and the Review of Literature2022

    • Author(s)
      Maekura Chika、Muramatsu Ayako、Nagata Hiroaki、Okamoto Haruya、Onishi Akio、Kato Daishi、Isa Reiko、Fujino Takahiro、Tsukamoto Taku、Mizutani Shinsuke、Shimura Yuji、Kobayashi Tsutomu、Okumura Keita、Inaba Tohru、Nukui Yoko、Kuroda Junya
    • Journal Title

      Infection and Drug Resistance

      Volume: Volume 15 Pages: 2723-2728

    • DOI

      10.2147/idr.s360238

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Rationale for the Dual-Targeting Therapy for RSK2 and AKT in Multiple Myeloma.2022

    • Author(s)
      Isa R, Horinaka M, Tsukamoto T, Mizuhara K, Fujibayashi Y, Taminishi-Katsuragawa Y, Okamoto H, Yasuda S, Kawaji-Kanayama Y, Matsumura-Kimoto Y, Mizutani S, Shimura Y, Taniwaki M, Sakai T, Kuroda J.
    • Journal Title

      Int J Mol Sci.

      Volume: 23 Issue: 6 Pages: 2919-2936

    • DOI

      10.3390/ijms23062919

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 26.Identification of novel tumour suppressor genes by using genome-wide in vivo CRISPR screening.2022

    • Author(s)
      水谷信介, Margaret A Potts, Lin Tai, Andrew J Kueh, Stephen Wilcox, 黒田 純也, Andreas Strasser, Marco J Herold.
    • Organizer
      第84回日本血液学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Efficacy of salvage therapy with carfilzomib followed by 2nd aPBSCT in relapse myeloma patients2021

    • Author(s)
      水谷信介
    • Organizer
      第46回日本骨髄腫学会学術集会
    • Related Report
      2021 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi