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Mechanistic analysis of drug-resistance in ALL

Research Project

Project/Area Number 17K10124
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Imamura Toshihiko  京都府立医科大学, 医学(系)研究科(研究院), 講師 (30444996)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords急性リンパ性白血病 / JAK-STAT / LNK / 薬剤耐性 / プレドニゾロン / ALL / ステロイド抵抗性 / SH2B3 / 薬剤耐性化機序 / LNK (SH2B3)
Outline of Final Research Achievements

Based on our hypothesis that JAK-STAT pathway is key for proliferation of lymphoblastic leukemic cells, we evaluated expressionlevel of LNK, which was negative regulator of JAK-STAT pathway and identified that low expression of LNK was associated with poor outcome (Yano M, Imamura T, et al. Br J Haematol 2017).
Next, we transduced Ba/F3 cells with LNK by retroviral gene transfer system, and identified that LNK induced dephosphorylation of JAK2-STAT5 and high sensitivity of prednisolone. However, loss of function mutant of LNK did not induce those phenomena. Primary patient's leukemic blasts with high expression of LNK also showed high sensitivity of PSL compared to those with low expression of LNK. These findings suggest that inhibition of JAK-STAT pathway might be therapeutic for high risk lymphoblastic leukemia.

Academic Significance and Societal Importance of the Research Achievements

我々の研究で、急性リンパ性白血病の細胞増殖に関わるJAK-STAT経路という箇所を抑制する事によって、ステロイドに代表される従来からの治療薬の効果が増すことが明らかとなった。
この事は、従来の薬剤の効果が乏しい急性リンパ性白血病にたいして、JAK-STAT経路を様々な手法で抑制する事が、薬剤の効果を高める可能性を示した点に学術的な意義があると考えられる。

Report

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

    (1 results)

All 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] Clinical significance of SH2B3 (LNK) expression in paediatric B-cell precursor acute lymphoblastic leukaemia2017

    • Author(s)
      Yano M, Imamura T, Asai D, Deguchi T, Hashii Y, Endo M, Sato A, Kawasaki H, Kosaka Y, Kato K, Hori H, Yumura-Yagi K, Hara J, Oda M, Horibe K.
    • Journal Title

      Br J Haematol

      Volume: - Issue: 2 Pages: 327-330

    • DOI

      10.1111/bjh.14981

    • Related Report
      2017 Research-status Report
    • Peer Reviewed

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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