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Lenalidomide as IKZF1 inhibitor induces Ph+ALL cells into apoptosis synergy with antileukemic agents

Research Project

Project/Area Number 16K19635
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionUniversity of Yamanashi

Principal Investigator

HARAMA Daisuke  山梨大学, 医学部附属病院, 医員 (10774078)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsフィラデルフィア染色体 / 急性白血病 / 新規治療法 / IKZF1 / 急性リンパ球性白血病 / レナリドミド / 急性リンパ性白血病 / フィラデルフィア染色体陽性急性急性リンパ性白血病 / Lenalidomide
Outline of Final Research Achievements

Combination use of lenalidomide (LEN) and imatinib (IM) on Philadelphia chromosome positive leukemia cell line showed synergistic antileukemic effect against using IM single agent. In addition, the same effect was further enhanced by using dexamethasone (DEX) in addition of LEN and IM. It was also observed that IKZF1 isoform was degraded in the presence of LEN, without mutated isoform Ik6, leading to be susceptible to TKI. This synergistic effect was also demonstrated in xenograft model using NOG mice. In comparison of mice without treatment, mice receiving LEN and IM longed survival time of approximately 180%.
LEN, IM, and DEX are all internal medicines, indicating the possibility of leading to a treatment that maintains QOL of leukemia patients.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2017 2016 Other

All Presentation (3 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Presentation] IKZF1阻害剤としてのレナリドミドは他剤との相乗作用でPh染色体陽性細胞にアポトーシスを誘導する2017

    • Author(s)
      原間大輔
    • Organizer
      第79回日本血液学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Lenalidomide induces apoptosis of Ph positive ALL cells in synergy with imatinib2016

    • Author(s)
      原間 大輔
    • Organizer
      第58回日本小児血液がん学会学術集会
    • Place of Presentation
      品川プリンスホテル(東京・品川)
    • Year and Date
      2016-12-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Lenalidomide Effectively Induces PhiladelphiaChromosome-Positive ALL Cellsinto Apoptosis in Synergy with Tyrosine Kinase Inhibitor2016

    • Author(s)
      Daisuke Harama
    • Organizer
      58th ASH Annual Meeting
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] ASH 58th Annual Meeting & Exposition

    • URL

      https://ash.confex.com/ash/2016/webprogram/Paper92026.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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