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Development of an evaluation method based on the elucidation of drug-resistance mechanisms of leukaemia cells through bone marrow niche cross talk

Research Project

Project/Area Number 18K07425
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionTokai University

Principal Investigator

MIYACHI Hayato  東海大学, 医学部, 教授 (20174196)

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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords白血病 / 抗がん剤抵抗性 / 細胞外マトリックス / 骨髄ニッチ / 抗がん剤治療 / 耐性 / 骨髄微小環境 / 抗がん剤耐性 / 遺伝子 / 急性白血病 / 骨髄(腔内)微小環境 / クロストーク
Outline of Final Research Achievements

In the treatment of acute leukemia patients, drug-resistance after therapy with chemotherapeutic agents is clinically problematic. The residual disease after the therapy survives and re-proliferates through bone marrow niche cross-talk. This study was undertaken to elucidate drug-resistance mechanisms of leukemia cells through bone marrow niche cross talk, and to development of an evaluation method based on it. Cultured leukemia cell lines with FLT3-ITD showed collateral resistance to are-C in the presence of fibronectin or G-CSF, which can derive from stromal cells in bone marrow. This crosstalk can be target of evaluation and interruption for the overcome.

Academic Significance and Societal Importance of the Research Achievements

急性白血病の治療において、抗がん剤に対する治療抵抗性(耐性)は患者診療上の重要な課題で、耐性の分子機構の解明とそれに基づく、診断と克服法への応用は治療成績の向上につながると期待される。治療後に残存した白血病細胞は、骨髄(腔内)微小環境(ニッチ)内に潜伏し、その再増殖が再発、治療抵抗性の原因となる。本研究では、治療後骨髄ニッチ内に残存し、予後不良の原因となる白血病細胞の耐性の分子機構を明らかにした。これらに重要な分子は、治療抵抗性の診断と治療法の開発を通して、個別患者に最も適切な治療法の選択と治療予後の改善に貢献しうると考えられる。

Report

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

    (5 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Attempts to optimize postinduction treatment in childhood acute myeloid leukemia without core-binding factors: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).2020

    • Author(s)
      Hasegawa D, Tawa A, Tomizawa D, Watanabe T, Saito AM, Kudo K, Taga T, Iwamoto S, Shimada A, Terui K, Moritake H, Kinoshita A, Takahashi H, Nakayama H, Koh K, Goto H, Kosaka Y, Miyachi H, Horibe K, Nakahata T, Adachi S.
    • Journal Title

      Pediatric Blood and Cancer

      Volume: 67 Issue: 12

    • DOI

      10.1002/pbc.28692

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simple screening method for the diagnosis of chronic myeloid leukemia using the parameters of a complete blood count and differentials2019

    • Author(s)
      Ogasawara A, Matsushita H, Tanaka Y, Shirasugi Y, Ando K, Asai S, Miyachi H
    • Journal Title

      Clinica Chimica Acta

      Volume: 489 Pages: 249-253

    • DOI

      10.1016/j.cca.2018.08.038

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term Remission of Acute Myeloid Leukemia Developed From Systemic Mastocytosis by Conventional Chemotherapy.2018

    • Author(s)
      2.Yamada A, Kinoshita M, Sawa D, Saito Y, Kamimura S, Miyachi H, Moritake H.
    • Journal Title

      J Pediatr Hematol Oncol.

      Volume: - Issue: 6 Pages: e402-e404

    • DOI

      10.1097/mph.0000000000001259

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of high-dose cytarabine in induction therapy for children with de novo acute myeloid leukemia: a study protocol of the Japan Children's Cancer Group Multi-Center Seamless Phase II-III Randomized Trial2018

    • Author(s)
      3.Tomizawa D, Tanaka S, Hasegawa D, Iwamoto S, Hiramatsu H, Kiyokawa N, Miyachi H, Horibe K, Saito AM, Taga T, Adachi S.
    • Journal Title

      Jpn J Clin Oncol.

      Volume: 48 Issue: 6 Pages: 587-593

    • DOI

      10.1093/jjco/hyy061

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] FLT3-ITD陽性白血病細胞のAra-C耐性におけるTGFB経路の役割(A role of TGFB pathway in Ara-C resistance in FLT3-ITD-positive leukemia cells)2019

    • Author(s)
      ナツァグドルジ・ムンホエルデネ, ダムディンスレン・アナラ , ツェウェグジャワ・バヤルバタ , ネメフバアタルラハスレン , 柿添 英文, 浅井 さとみ, 宮地 勇人
    • Organizer
      第66回 日本臨床検査医学会学術集会
    • Related Report
      2019 Research-status Report

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

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