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Functional analysis of STAP, a signal-regulating molecule, in clonal expansion of myeloproliferative tumor stem cells

Research Project

Project/Area Number 21K16243
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Toda Jun  大阪大学, 大学院医学系研究科, 招へい教員 (90770834)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsSTAP / MPN / STAP蛋白
Outline of Research at the Start

骨髄増殖性疾患(MPN)は造血幹細胞レベルの腫瘍化によって発症する疾患である。最近、申請者はSignal transducing adaptor protein (STAP) -1が、アダプター蛋白として炎症系シグナルを介し、STAT5のリン酸化を制御することでCML幹細胞の生存に関わっていることを報告した。本研究ではCML以外のBCR-ABL陰性MPNに焦点を絞り、STAP蛋白がMPNの病態に及ぼす影響とそのメカニズムの解明を目的とした。この検討により、MPN幹細胞を標的とした薬剤開発などの臨床応用への発展の土台を作ることが本研究の目的である。

Outline of Final Research Achievements

To investigate whether STAP family molecules are essential for the maintenance of leukemia stem cells other than those in CML, and to establish a therapeutic foundation targeting MPN stem cells, we conducted studies using MPN model mice. Initially, we transplanted bone marrow from JAK2V617F knock-in mice into WT mice and confirmed the MPN phenotype. Subsequently, bone marrow cells from WT, JAK2TG, and JAK2TG/STAP2KO mice were transplanted into irradiated recipient mice. The STAP2KO mice exhibited a higher white blood cell count, more severe anemia, and thrombocytopenia compared to the JAK2TG mice, along with an increase in LK cells. These findings suggest that STAP-2 deficiency may promote the progression of MPN. In contrast, in similar experiments with STAP1KO mice, no significant differences were observed in peripheral blood, bone marrow, or spleen cells. This indicates that while STAP-1 plays a functional role in stem cells in CML, it does not significantly affect MPN stem cells.

Academic Significance and Societal Importance of the Research Achievements

本研究は、白血病幹細胞の維持に必要なSTAPファミリー分子の役割を明らかにし、特にSTAP-2がMPNの進行に寄与する可能性を示しました。この発見は、MPN治療の新たなターゲットを提供し、より効果的な治療法の開発に繋がります。社会的には、白血病患者の生活の質向上と治療成績の向上に寄与し、医療費の削減にも貢献する可能性があります。研究成果は、白血病治療の新たな方向性を示し、将来の臨床応用に大きな期待を寄せています。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (3 results)

All 2024 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Role of Signal-Transducing Adaptor Protein-1 for T Cell Activation and Pathogenesis of Autoimmune Demyelination and Airway Inflammation2024

    • Author(s)
      Kagohashi Kota、Sasaki Yuto、Ozawa Kiyotaka、Tsuchiya Takuya、Kawahara Shoya、Saitoh Kodai、Ichii Michiko、Toda Jun、Harada Yasuyo、Kubo Masato、Kitai Yuichi、Muromoto Ryuta、Oritani Kenji、Kashiwakura Jun-ichi、Matsuda Tadashi
    • Journal Title

      The Journal of Immunology

      Volume: 212 Issue: 6 Pages: 951-961

    • DOI

      10.4049/jimmunol.2300202

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signal-transducing adaptor protein-1 and protein-2 in hematopoiesis and diseases2022

    • Author(s)
      Ichii, Michiko; Oritani, Kenji; Toda, Jun; Hosen, Naoki; Matsuda, Tadashi; Kanakura, Yuzuru
    • Journal Title

      Experimental Hematology

      Volume: 105 Pages: 10-17

    • DOI

      10.1016/j.exphem.2021.11.002

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive interactions between STAP-1 and BCR-ABL influence chronic myeloid leukemia cell proliferation and survival2021

    • Author(s)
      Ishiura, Marie; Kitai, Yuichi; Kashiwakura, Jun-ichi; Muromoto, Ryuta; Toda, Jun; Ichii, Michiko; Oritani, Kenji; Matsuda, Tadashi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 556 Pages: 185-191

    • DOI

      10.1016/j.bbrc.2021.03.162

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

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Published: 2021-04-28   Modified: 2025-01-30  

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