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regulation of autophagy flux in megakaryocyte-platelet lineage

Research Project

Project/Area Number 19K08873
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 InstitutionIwate Medical University

Principal Investigator

Kowata Shugo  岩手医科大学, 医学部, 講師 (30418884)

Co-Investigator(Kenkyū-buntansha) 佐々木 了政  岩手医科大学, 医学部, 助教 (40825501)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords血小板産生 / autophagy / 血小板 / 巨核球 / JAK2遺伝子変異 / PDL-1 / proplatelet / thrombopoiesis / mitchondria / Autophagy / platelet production
Outline of Research at the Start

血小板は止血機能に重要な細胞です。一方血小板は脳梗塞や心筋梗塞を生じる引き金の一つでもあることも解っています。通常、骨髄で産生された血小板は血液中で7日間働いたのちに寿命を終えます。今回の研究は、血小板が生まれ寿命を終えるまでに、autophagyが血小板内でどのような働きをしているかを研究します。その結果、血小板が関連する特定の病気を見つける検査法や、治療の手がかりを掴むことが期待されます。

Outline of Final Research Achievements

In our studies of mice, autophagosome-rich platelets (ARPs), which possess autophagosomes detectable by the electron microscopic assay and the cationic fluorescent dye Cyto-ID, were increased in nascent platelets and proplatelet fragments . The dynamics of the proportion of ARPs (ARPs%) parallels that of RPs%, implying that ARPs are young platelets. To determine this property in human, we measured the proportion of ARPs% in patients with thrombocytopenia, including immune thrombocytopenia(ITP). We examined 34 patients with ITP and 52 patients with other types of thrombocytopenic disorders. Among thrombocytopenic patients, ARPs% was significantly elevated only in ITP patients (P<0.01). These data suggest that enhanced autophagy of platelets is a characteristic finding in patients with ITP and shows diagnostic potential in thrombocytopenia.

Academic Significance and Societal Importance of the Research Achievements

本研究結果は、一つの巨核球(血小板産生細胞)が、数千の血小板を短時間で産生する際に、一旦ばらばらの大きさの血小板が放出されるが短時間のうちに、均一な血小板に変化している現象について、autophagy(細胞内の自食装置)が大きく関わっている事を示した。ついでこの現象を臨床検体で把握することにより、ヒトの血小板減少症において、臨床的に原因を調べる手掛かりとなりうることを示した。今後、血小板が関わる他の疾病(血栓症、脳卒中、白血病など)における、創薬(血栓予防薬や血小板数抑制薬)、検査法(血小板産生状況、血小板の未熟さや血栓傾向の程度)の理解が進む足場となる成果が得られた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2021 2020

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

  • [Journal Article] Acute Liver Injury Due to T-cell Infiltration into the Liver as an Initial Clinical Finding of Adult T-cell Leukemia/Lymphoma2021

    • Author(s)
      Keisuke,Kakisaka.,Yuji,Suzuki.,Shugo,Kowata.,Shigeki,Ito.,Yasuhiro,Takikawa.
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 15 Pages: 2431-2436

    • DOI

      10.2169/internalmedicine.6793-20

    • NAID

      130008070621

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-08-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of secondary engraftment failure with granulocyte colony-stimulating factor and eltrombopag after allogeneic peripheral blood stem cell transplantation in adult T-cell leukemia/lymphoma2021

    • Author(s)
      清原千貴,菅原教史,前田峻大,宮島真理,高野幹,西谷匡央,西谷真来,佐々木了政,岡野良昭,上原さつき,古和田周吾,小宅達郎,伊藤薫樹
    • Journal Title

      Rinsho Ketsueki

      Volume: 62 Issue: 10 Pages: 1499-1504

    • DOI

      10.11406/rinketsu.62.1499

    • NAID

      130008113175

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] JAK2V617 変異を伴う骨髄増殖性腫瘍の変異クローンの拡大はPD-1陽性CD8陽性細胞の減少を伴う2021

    • Author(s)
      宮島真理、古和田周吾、
    • Journal Title

      岩手医学雑誌

      Volume: 73

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagosome-rich Platelets are increased in immune thrombocytopenia.2020

    • Author(s)
      Akihiro,Otsu.,Shugo,Kowata.,Yuki,Seki.,Kazunori,Murai.,Kazuki,Kiyohara.,Shinri,Miyajima.,Wataru,Izumita.,Jiro,Hitomi.,Yoji,Ishida.,Shigeki,Ito.
    • Journal Title

      Journal of Iwate Medical Association

      Volume: 72 Pages: 103-113

    • NAID

      130007898058

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment-free remission after ffirst-line dasatinib discontinuation in patients with chronic myeloid leukaemia2020

    • Author(s)
      Kimura S, Imagawa J, Murai K, Hino M, Kitawaki T, Okada M, Tanaka H, Shindo M, Kumagai T, Ikezoe T, Uoshima N, Sato T, Watanabe R, Kowata S, Hayakawa M, Hosoki T, Ikeda K
    • Journal Title

      Lancet Haematol.

      Volume: 7 Pages: 218-225

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Doripenem versus meropenem as first-line empiric therapy of febrile neutropenia in patients with acute leukemia: a prospective, randomized study.2020

    • Author(s)
      Oyake T, Takemasa-Fujisawa Y, Sugawara N, Mine T, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata S, Ito S, Ishida Y.:
    • Journal Title

      Ann. Hematol

      Volume: 98 Pages: 1209-1216

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autophagosome rich platelet2020

    • Author(s)
      Akihiro Otsu, Kowata Shugo, Yuki Seki, et.al
    • Journal Title

      Iwate Medical Journal

      Volume: 67 Pages: 225230-225230

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] PD-1 positive CD8+T-cells and allele burden in JAK2V617 positive MPNs2021

    • Author(s)
      宮島真理、古和田周吾、岡野良昭、小宅達郎、伊藤薫樹
    • Organizer
      第83回日本血液学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Retrospective analysis of ICI therapy for r/r classical lymphoma:THP262021

    • Author(s)
      前田峻大、岡野良昭、古和田周吾、小宅達郎、伊藤薫樹
    • Organizer
      第83回日本血液学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Usefulness of presepsin as a diagnostic biomarker of HPS associated with hematological disease2021

    • Author(s)
      岡野良昭,小宅達郎,浅野雄哉,佐藤剛,清原千貴,西谷真来,菅原教史,佐々木了政,古和田周吾,伊藤薫樹
    • Organizer
      第83回日本血液学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Stauprimide induces mitotic cell cycle arrest and apoptosis in multiple myeloma2021

    • Author(s)
      清原千貴,西谷真来,菅原教史,佐々木了政,古和田周吾,伊藤薫樹
    • Organizer
      第83回日本血液学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ドナーリンパ球輸注が奏効した血縁者間同種造血幹細胞移植後の播種性アデノウイルス感染症の一例2021

    • Author(s)
      宮島真理,菅原教史,浅野雄哉,前田峻大,清原千貴,高野幹,西谷真来,佐々木了政,岡野良昭,古和田周吾,小宅達郎,伊藤薫樹
    • Organizer
      第83回日本血液学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Autophagosome-rich platelets are increased in patients with immune thrombocytopenia.2020

    • Author(s)
      Akihiro Otsu, Shugo Kowata,Yuki Seki,Kazunori Murai, Kazuki Kiyohara, Shinri Miyajima, Wataru Izumita, Jiro Hitomi, Yoji Ishida, Shigeki Ito.
    • Organizer
      25st European Hematology Association (EHA)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Autophagosome rich platelets are increased in patients with ITP2020

    • Author(s)
      Akihiro Otsu, Shugo Kowata, Yuki Seki, et.al
    • Organizer
      Europian Hematology Association
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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