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15-PGDH regulates leukemia stem cell potential in HOX-associated myeloid leukemia

Research Project

Project/Area Number 17H03579
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionTokyo Women's Medical University (2018-2019)
Kumamoto University (2017)

Principal Investigator

Iwasaki Masayuki  東京女子医科大学, 医学部, 講師 (70790913)

Co-Investigator(Kenkyū-buntansha) 山本 浩平  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50451927)
大里 元美  熊本大学, 国際先端医学研究機構, 特別招聘教授 (90314286)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywords白血病幹細胞 / 15-PGDH / MEIS1 / HOX / MLL
Outline of Final Research Achievements

In the present study, we investigated the function of 15-PGDH, prostaglandin-degrading enzyme in HOX-associated leukemia stem cells. We found that 15-PGDH had an alternative function to promote oncogenesis in addition to its previously characterized tumor suppressor role. We also demonstrated that 15-PGDH was required for initiation and maintenance of MLL-mediated myeloid transformation, and 15-PGDH non-enzymatically regulated the leukemia stem cell potential. These findings provide a foundation to develop novel molecular targeted therapies for refractory hematological malignancies.

Academic Significance and Societal Importance of the Research Achievements

15-PGDHは大腸癌や肺癌などの固形腫瘍においてがん抑制遺伝子として機能しているが、最近、15-PGDHはマウスモデルにおいて骨髄、大腸、肝臓の再生および修復に対し、負の働きをしていることが報告されて注目されている。本研究により、HOX関連白血病において15-PGDHは発症促進に働いており、他の腫瘍とは異なるメカニズムによって発がんに関与していることを見出した。これらの成果は、がんや再生医療における分子標的治療の開発を進める上で非常に意義があるものと思われる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (10 results)

All 2019 2018 2017 Other

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

  • [Int'l Joint Research] Stanford University School of Medicine(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Stanford University School of Medicine(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Stanford University School of Medicine(米国)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] MicroRNA-127-3p controls murine hematopoietic stem cell maintenance by limiting differentiation2019

    • Author(s)
      Crisafulli Laura、Muggeo Sharon、Uva Paolo、Wang Yulei、Iwasaki Masayuki、Locatelli Silvia、Anselmo Achille、Colombo Federico S.、Carlo-Stella Carmelo、Cleary Michael L.、Villa Anna、Gentner Bernhard、Ficara Francesca
    • Journal Title

      Haematologica

      Volume: 104 Issue: 9 Pages: 1744-1755

    • DOI

      10.3324/haematol.2018.198499

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High-efficiency CRISPR induction of t(9;11) chromosomal translocations and acute leukemias in human blood stem cells2019

    • Author(s)
      Jeong Johan、Jager Astraea、Domizi Pablo、Pavel-Dinu Mara、Gojenola Linda、Iwasaki Masayuki、Wei Michael C.、Pan Feng、Zehnder James L.、Porteus Matthew H.、Davis Kara L.、Cleary Michael L.
    • Journal Title

      Blood Advances

      Volume: 3 Issue: 19 Pages: 2825-2835

    • DOI

      10.1182/bloodadvances.2019000450

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MLL leukemia induction by t(9;11) chromosomal translocation in human hematopoietic stem cells using genome editing2018

    • Author(s)
      Schneidawind Corina、Jeong Johan、Schneidawind Dominik、Kim In-Suk、Duque-Afonso Jesus、Wong Stephen Hon Kit、Iwasaki Masayuki、Breese Erin H.、Zehnder James L.、Porteus Matthew、Cleary Michael L.
    • Journal Title

      Blood Advances

      Volume: 2 Issue: 8 Pages: 832-845

    • DOI

      10.1182/bloodadvances.2017013748

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Essential non-canonical role for 15-PGDH in MLL-rearranged AML stem cells2019

    • Author(s)
      Masayuki Iwasaki
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Essential non-canonical role for 15-PGDH in HOX-associated leukemia stem cells2019

    • Author(s)
      Masayuki Iwasaki
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] MLL遺伝子再構成をを伴う急性骨髄性白血病幹細胞における15-PGDHの役割2017

    • Author(s)
      岩崎正幸, Michael Cleary
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Book] MLL遺伝子再構成陽性急性骨髄性白血病幹細胞におけるCD93の発現(血液内科)2017

    • Author(s)
      岩崎正幸
    • Total Pages
      6
    • Publisher
      科学評論社
    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-05-23  

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