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

Development of novel therapeutic strategies for myeloproliferative neoplasms caused by mutant CALR

Research Project

Project/Area Number 18K08372
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 InstitutionJuntendo University

Principal Investigator

Yang Yinjie  順天堂大学, 医学部, 特任助教 (90808643)

Co-Investigator(Kenkyū-buntansha) 小松 則夫  順天堂大学, 医学部, 教授 (50186798)
今井 美沙  順天堂大学, 医学(系)研究科(研究院), 非常勤助教 (50709003)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords骨髄増殖性腫瘍 / mutant CALR / 低分子化合物 / 変異型CALR / calreticulin
Outline of Final Research Achievements

In this study, by use of myeloproliferative neoplasms (MPNs) model cell lines and animals, we analyzed a small molecule (compound X) with high tumor cell selectivity obtained by compound library screening using a cell line proliferating in a manner dependent on mutant calreticulin that was found in patients with MPNs. As a result, it was found that compound X is promising as a drug candidate molecule.

Academic Significance and Societal Importance of the Research Achievements

骨髄増殖性腫瘍(MPN)は、造血幹細胞に体細胞変異が生じることで引き起こされる造血器の腫瘍である。最新の分子標的薬を用いても寛解には至らず、根治は、治療関連死のリスクのある造血幹細胞移植に限られていることから、根治を目指した有効な治療薬の開発が切望されている。本研究により明らかにされた医薬候補分子を基盤としてMPNの根治を可能にする治療薬の開発が大いに期待される。

Report

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

    (15 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] CREB3L1 overexpression as a potential diagnostic marker of Philadelphia chromosome?negative myeloproliferative neoplasms2020

    • Author(s)
      Morishita Soji、Yasuda Hajime、Yamawaki Saya、Kawaji Hideya、Itoh Masayoshi、Edahiro Yoko、Imai Misa、Kogo Yasushi、Tsuneda Satoshi、Ohsaka Akimichi、Hayashizaki Yoshihide、Ito Masafumi、Araki Marito、Komatsu Norio
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 2 Pages: 884-892

    • DOI

      10.1111/cas.14763

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interferon therapy for pregnant patients with essential thrombocythemia in Japan2020

    • Author(s)
      Edahiro Yoko、Yasuda Hajime、Gotoh Akihiko、Morishita Soji、Suzuki Toshifumi、Takeda Jun、Ando Jun、Tsutsui Miyuki、Itakura Atsuo、Komatsu Norio
    • Journal Title

      International Journal of Hematology

      Volume: 113 Issue: 1 Pages: 106-111

    • DOI

      10.1007/s12185-020-03001-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism underlying the development of myeloproliferative neoplasms through mutant calreticulin2020

    • Author(s)
      Edahiro Yoko、Araki Marito、Komatsu Norio
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 8 Pages: 2682-2688

    • DOI

      10.1111/cas.14503

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mutant calreticulin interacts with MPL in the secretion pathway for activation on the cell surface2019

    • Author(s)
      Masubuchi Nami、Araki Marito、Yang Yinjie、Hayashi Erina、Imai Misa、Edahiro Yoko、Hironaka Yumi、Mizukami Yoshihisa、Kihara Yoshihiko、Takei Hiraku、Nudejima Mai、Koike Masato、Ohsaka Akimichi、Komatsu Norio
    • Journal Title

      Leukemia

      Volume: 34 Issue: 2 Pages: 499-509

    • DOI

      10.1038/s41375-019-0564-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Homomultimerization of mutant calreticulin is a prerequisite for MPL binding and activation2018

    • Author(s)
      Araki Marito、Yang Yinjie、Imai Misa、Mizukami Yoshihisa、Kihara Yoshihiko、Sunami Yoshitaka、Masubuchi Nami、Edahiro Yoko、Hironaka Yumi、Osaga Satoshi、Ohsaka Akimichi、Komatsu Norio
    • Journal Title

      Leukemia

      Volume: 33 Issue: 1 Pages: 122-131

    • DOI

      10.1038/s41375-018-0181-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis of behavior of erythropoietin receptor on the cell surface in JAK2 mutant cells.2020

    • Author(s)
      Shioiri K, Araki M, Kitazawa S, Masubuchi N, Morishita S, Imai M, Ohsaka A, Komatsu N.
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] CREB3L1 overexpression as a novel diagnostic marker of myeloproliferative neoplasms.2020

    • Author(s)
      Morishita S, Yasuda H, Yamawaki S, Kawaji H, Itoh M, Edahiro Y, Imai M, Kogo Y, Tsuneda S, Ohsaka A, Hayashizaki Y, Araki M, Komatsu N.
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Therapeutic potential of myeloproliferative neoplasms by antibody targeting mutant calreticulin.2020

    • Author(s)
      Kihara Y, Araki M, Imai M, Fukuda Y, Mori Y, Taguchi T, Masubuchi N, Mabuchi Y, Yang Y, Mizukami Y, Morishita S, Akazawa C, Ohsaka A, Komatsu N.
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 変異型CALRはMPLと分泌経路で相互作用し細胞表面で活性化を引き起こす.2019

    • Author(s)
      増渕菜弥, 荒木真理人, 楊印杰, 林英里奈, 今井美沙, 枝廣陽子, 弘中由美, 水上喜久, 木原慶彦, 小池正人, 大坂顯通, 小松則夫.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 変異型calreticulin特異的配列によるゴルジ体への局在.2019

    • Author(s)
      水上喜久, 荒木真理人, 今井美沙, 林英里奈, 増渕菜弥, 楊印杰, 木原慶彦, 弘中由美, 大坂顯通, 小松則夫.
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 分泌経路における変異型分子シャぺロンとサイトカイン受容体の会合による細胞の腫瘍化.2019

    • Author(s)
      増渕菜弥, 荒木真理人, 木原慶彦, 楊印杰, 今井美沙, 水上喜久, 林英里奈, 弘中由美, 竹井拓, 枝廣陽子, 大坂顯通, 小松則夫.
    • Organizer
      第29回日本サイトメトリー学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 変異型特異的配列による変異型CALRの細胞内局在の規定.2019

    • Author(s)
      水上喜久, 荒木真理人, 今井美沙, 林絵里奈, 増渕菜弥, 楊印杰, 木原慶彦, 弘中由美, 大坂顯通, 小松 則夫.
    • Organizer
      第29回日本サイトメトリー学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] トリプルネガティブ本態性血小板血症症例の臨床像と遺伝子変異.2018

    • Author(s)
      稲野資明, 荒木真理人, 福田泰隆, 森下総司, 落合友則, 三澤恭平, 伊藤雅文, 山本紘司, 楊印杰, 田口鉄平, 枝廣陽子, 今井美沙, 後藤明彦, 大坂顯通, 小松則夫.
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 変異型 CALRの多量体化は MPLとの結合と活性化に必須である.2018

    • Author(s)
      荒木真理人, 楊印杰, 今井美沙, 水上喜久, 木原慶彦, 角南義孝, 増渕菜弥, 枝廣陽子, 弘中由美, 大佐賀智, 大坂顯通, 小松則夫.
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Boarding on the secretary pathway is required for the oncogenic property of mutant calreticulin.2018

    • Author(s)
      Araki M, Masubuchi N, Hayashi E, Yang Y, Imai M, Kihara Y, Mizukami Y, Hironaka Y, Edahiro Y, Ohsaka A, Komatsu N.
    • Organizer
      23rd Congress of the European Hematology Association
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi