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CRISPR screening for identification of molecular targets of T/NK cell lymphomas

Research Project

Project/Area Number 18K08313
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionHokkaido University

Principal Investigator

Nakagawa Masao  北海道大学, 医学研究院, 助教 (80435859)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsT細胞リンパ腫 / NK細胞リンパ腫 / ATLL / CRISPR / 分子標的治療 / T/NK細胞リンパ腫 / CRISPRスクリーニング / T細胞性リンパ腫 / NK細胞性リンパ腫
Outline of Final Research Achievements

In this study, we performed genome-wide CRISPR-Cas9 screens in multiple T/NK lymphoma cell lines for identifying essential genes for cellular proliferation/survival in a series of T/NK cell lymphoma cell lines. Positive and negative control sgRNAs were correctly identified through the entire screening, confirming the validity of the screening results. We identified genes which were selectively essential for each diease group in T/NK cell lymphomas. Some among the essential genes were confirmed in the follow-up functional experiments. All together, we established an entire list of candidate genes for molecular targeted therapies in T/NK cell lymphomas.

Academic Significance and Societal Importance of the Research Achievements

T/NK細胞リンパ腫の多くは現行の治療に対して5年生存率30%と予後不良である。今回の研究からT/NK細胞リンパ腫の治療標的分子・分子シグナリングの包括的リストを作成できたことで、新規分子標的治療開発が加速され、将来的にT/NK細胞リンパ腫の治療成績の向上に貢献することができる。また、T/NK細胞リンパ腫の増殖・生存の分子メカニズムの理解が進んだ点は学術的意義が高い。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (26 results)

All 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Remarks (2 results)

  • [Int'l Joint Research] National Cancer Institute, NIH/Fox Chase Cancer Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Fox Chase Cancer Center/National Institutes of Health(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Fox Chase Cancer Center/National Institutes of Health(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] A novel model of alternative NF-κB pathway activation in anaplastic large cell lymphoma2020

    • Author(s)
      Wang Hongbo、Wei Wei、Zhang Jing-Ping、Song Zhihui、Li Yangyang、Xiao Wenming、Liu Yijun、Zeng Mu-Sheng、Petrus Michael N.、Thomas Craig J.、Kadin Marshall E.、Nakagawa Masao、Waldmann Thomas A.、Yang Yibin
    • Journal Title

      Leukemia

      Volume: - Issue: 7 Pages: 1976-1989

    • DOI

      10.1038/s41375-020-01088-y

    • Related Report
      2020 Annual Research Report
  • [Journal Article] A novel model of controlling PD-L1 expression in ALK+ Anaplastic Large Cell Lymphoma2019

    • Author(s)
      Zhang, JP., Song, Z., Wang, HB., Lang, L., Yang YZ., Xiao, W., Webster, DE., Wei, W., Barta, SK., Kadin, ME., Staudt, LM., Nakagawa, M., and Yang, Y.
    • Journal Title

      Blood

      Volume: 132 Issue: 2 Pages: 171-185

    • DOI

      10.1182/blood.2019001043

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD.2019

    • Author(s)
      Ohigashi, H., Hashimoto, D., Hayase, E., Takahashi, S., Ara, T., Yamakawa, T., Sugita, J., Onozawa, M., Nakagawa, M., Teshima, T.
    • Journal Title

      Blood Adv.

      Volume: 3 Issue: 7 Pages: 1003-1010

    • DOI

      10.1182/bloodadvances.2018028431

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting the HTLV-I-Regulated BATF3/IRF4 Transcriptional Network in Adult T Cell Leukemia/Lymphoma2018

    • Author(s)
      Nakagawa M, Shaffer AL, Ceribelli M, Zhang M, Wright G, Huang DW, Xiao W, Powell J, Petrus MN, Yang Y, Phelan JD, Kohlhammer H, Dubois SP, Yoo HM, Bachy E, Webster DE, Yang Y,Xu W, Yu X, Zhao H, Bryant BR, Shimono J, Ishio T, Maeda M, Green PL, Waldmann TA , Staudt LM.
    • Journal Title

      Cancer Cell

      Volume: 34 Issue: 2 Pages: 286-297.e10

    • DOI

      10.1016/j.ccell.2018.06.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The association between the incidence of intestinal graft-vs-host disease and antibiotic use after allogeneic hematopoietic stem cell transplantation2018

    • Author(s)
      Hidaka Daisuke、Hayase Eiko、Shiratori Souichi、Hasegawa Yuta、Ishio Takashi、Tateno Takahiro、Okada Kohei、Goto Hideki、Sugita Junichi、Onozawa Masahiro、Nakagawa Masao、Kahata Kaoru、Endo Tomoyuki、Hashimoto Daigo、Teshima Takanori
    • Journal Title

      Clinical Transplantation

      Volume: 32 Issue: 9

    • DOI

      10.1111/ctr.13361

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A multiprotein supercomplex controlling oncogenic signalling in lymphoma2018

    • Author(s)
      Phelan JD, Young RM, Webster DE, Roulland S, Wright GW, Kasbekar M, Shaffer AL, Ceribelli M, Wang JQ, Schmitz R, Nakagawa M, Bachy E, Huang DW, Ji Y, Chen L, Yang Y, Zhao H, Yu X, Xu W, Palisoc MM et al.
    • Journal Title

      Nature

      Volume: 560 Issue: 7718 Pages: 387-391

    • DOI

      10.1038/s41586-018-0290-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia2018

    • Author(s)
      Hashiguchi Junichi、Onozawa Masahiro、Oguri Satoshi、Fujisawa Shinichi、Tsuji Masahisa、Okada Kohei、Nakagawa Masao、Hashimoto Daigo、Kahata Kaoru、Kondo Takeshi、Shimizu Chikara、Teshima Takanori
    • Journal Title

      The Journal of Molecular Diagnostics

      Volume: 20 Issue: 4 Pages: 446-454

    • DOI

      10.1016/j.jmoldx.2018.02.005

    • NAID

      120006649182

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hematogones Predict Better Outcome in Allogeneic Hematopoietic Stem Cell Transplantation Irrespective of Graft Sources2018

    • Author(s)
      Ishio Takashi、Sugita Junichi、Tateno Takahiro、Hidaka Daisuke、Hayase Eiko、Shiratori Souichi、Okada Kohei、Goto Hideki、Onozawa Masahiro、Nakagawa Masao、Hashimoto Daigo、Kahata Kaoru、Fujimoto Katsuya、Endo Tomoyuki、Kondo Takeshi、Teshima Takanori
    • Journal Title

      Biology of Blood and Marrow Transplantation

      Volume: 24 Issue: 10 Pages: 1990-1996

    • DOI

      10.1016/j.bbmt.2018.06.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin αIIbβ3 in autosomal dominant macrothrombocytopenia with aggregation dysfunction2018

    • Author(s)
      Miyashita Naohiro、Onozawa Masahiro、Hayasaka Koji、Yamada Takahiro、Migita Ohsuke、Hata Kenichiro、Okada Kohei、Goto Hideki、Nakagawa Masao、Hashimoto Daigo、Kahata Kaoru、Kondo Takeshi、Kunishima Shinji、Teshima Takanori
    • Journal Title

      Annals of Hematology

      Volume: 97 Issue: 4 Pages: 629-640

    • DOI

      10.1007/s00277-017-3214-4

    • NAID

      120006600942

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Genome-wide CRISPR screen identifies CDK6 and mTORC1 as a combinatorial therapeutic target in ATLL2020

    • Author(s)
      Takashi Ishio, Sarvesh Kumar, Joji Shimono, Yuquan Lin, Emmanuel Bachy, Michael N. Petrus, Yandan Yang, Michiyuki Maeda, Hideki Goto, Satoshi Hashino, Takanori Teshima, Thomas A. Waldmann, Louis M. Staudt, Masao Nakagawa
    • Organizer
      日本血液学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Analysis of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in PTCL2020

    • Author(s)
      千葉雅尋、下埜城嗣、横田勲、重松明男、太田秀一、小林一、堤豊、山本聡、黒澤光俊、柿木康孝、近藤健、岩崎博、酒井基、宮城島拓人、長谷山美仁、永嶋貴博、國枝保幸、石尾崇、後藤秀樹、橋野聡、松野吉宏、中川雅夫、豊嶋崇徳
    • Organizer
      日本血液学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Genome-Wide Crispr Library Screening identifies genetic vulnerabilities and therapeutic targets in adult T-cell leukemia/lymphoma2020

    • Author(s)
      Takashi Ishio, Sarvesh Kumar, Joji Shimono, Yuquan Lin, Emmanuel Bachy, Michael N. Petrus, Yandan Yang, Michiyuki Maeda, Hideki Goto, Satoshi Hashino, Takanori Teshima, Thomas A. Waldmann, Louis M. Staudt, Masao Nakagawa
    • Organizer
      25th EHA Virtual
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The combination of the CDK4/6 inhibitor palbociclib with mTOR inhibitors showed addivity in the treatment of HTLV-1 associated adult T-cell leukemia2020

    • Author(s)
      Takashi Ishio, Sarvesh Kumar, Thomas A. Waldmann and Masao Nakagawa
    • Organizer
      the 12th Annual T-cell Lymphoma Forum
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genome-Wide CRISPR Library Screening Identifies CDK6 As Genetic Vulnerability in Adult T-Cell Leukemia/Lymphoma.2019

    • Author(s)
      Takashi Ishio, Joji Shimono, Sarvesh Kumar, Yuquan Lin, Emmanuel Bachy, Michael N. Petrus, Yandan Yang, Michiyuki Maeda, Hideki Goto, Hashino Satoshi, Takanori Teshima, Thomas A. Waldmann, Louis M. Staudt, and Masao Nakagawa
    • Organizer
      61st ASH Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] BATF3/IRF4 transcriptional complex suppresses cellular immunity-associated gene signature in HTLVI-associated ATLL cells2019

    • Author(s)
      Masao Nakagawa, Joji Shimono, Takashi Ishio, Takanori Teshima
    • Organizer
      The 78th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2019 Research-status Report
  • [Presentation] Clinicopathological analysis of BATF3 and IRF4 in PTCL2019

    • Author(s)
      下埜 城嗣、石尾崇、後藤秀樹、堤豊、盛暁生、小林一、黒澤光俊、柿木康孝、重松明男、太田秀一、酒井基、宮城島拓人、長谷山美仁、岩﨑博、山本聡、國枝 保幸、橋野聡、三好寛明、大島孝一、畑中 豊、松野吉宏、中川雅夫、豊嶋崇徳
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] "Targeting the HTLV-I-regulated BATF3/IRF4 Transcriptional Network in Adult T-Cell Leukemia/Lymphoma"2019

    • Author(s)
      Nakagawa M.
    • Organizer
      "The 34th Nagoya International Cancer Treatment Symposium"
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanisms of HBZ for ATLL cell proliferation2018

    • Author(s)
      Nakagawa M, Endo T, Teshima T, Waldmann TA, Staudt LM
    • Organizer
      The 28th annual Meeting of the Japanese Association for Antiviral Therapy
    • Related Report
      2018 Research-status Report
  • [Presentation] Critical roles of BATF3/IRF4 in PTCL pathogenesis2018

    • Author(s)
      Nakagawa M.
    • Organizer
      The 58th Annual Meeting of the Japanese Society for Lymphoreticular Tissue Research.
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Recent advances of molecular pathogenesis of B-cell lymphomas2018

    • Author(s)
      Nakagawa M.
    • Organizer
      The 77th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] PTCL におけるBATF3/IRF42018

    • Author(s)
      Nakagawa M.
    • Organizer
      第4 回リンパ腫分子病態研究会 沖縄シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] 北海道大学大学院医学研究院 血液内科学教室 リンパ系腫瘍グループ

    • URL

      http://www.hokudai-hematology.jp/medical/basic-research/index3.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 北海道大学大学院 医学研究院 血液内科 リンパ系腫瘍研究グループ

    • URL

      http://www.hokudai-hematology.jp/medical/basic-research/index3.html

    • Related Report
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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