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Clinical potentiality of high expression of EVI1 and MEL1 in pediatric AML

Research Project

Project/Area Number 16K10052
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNational Cancer Center Japan

Principal Investigator

Ichikawa Hitoshi  国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (30201924)

Research Collaborator MITANI sachiyo  
YAMAZAKI fumito  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords小児AML / 小児急性骨髄性白血病 / 予後マーカー / 治療選択マーカー / EVI1 / MEL1 / nCounter / 臨床検査 / AML / 小児白血病 / 予後因子 / 治療選択 / バイオマーカー / 遺伝子発現
Outline of Final Research Achievements

Microarray analysis of the AML99 study patients showed that the high expression of the EVI1 or MEL1 genes was significantly associated with inferior survival. Their high expression was expected to be a good biomarker for therapy stratification. However, the qRT-PCR assay potentially has a risk of systematic error or bias derived from cDNA synthesis and enzymatic amplification, and is not easy to use in clinical settings. As a more practical testing method, we evaluated the nCounter system that directly measure target mRNA molecules without cDNA synthesis or enzymatic amplification. Our evaluation revealed high concordance between the nCounter assay and the qRT-PCR or microarray assay, and reproducibility of the nCounter assay. These results indicate that nCounter assay is a reliable and reproducible method to assess high EVI1 or MEL1 expression in AML patients.

Academic Significance and Societal Importance of the Research Achievements

小児AMLにおいてEVI1/MEL1高発現症例は極めて予後不良であるが、第一寛解期に同種造血幹細胞移植を行った場合に生存例が多く認められ、造血幹細胞移植治療を行うことで予後がかなり改善されることが示唆されている。通常遺伝子発現をバイオマーカーとして使用することには再現性の面から困難な場合が多いが、nCounterシステムを用いることで安定した検査が可能であることが示された。実際に治療層別化マーカーとして臨床導入することで、小児AMLの予後の改善が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (1 results)

All 2017

All Presentation (1 results)

  • [Presentation] 小児AMLにおけるnCounterを用いたEVI1/PRDM16発現解析の臨床応用の検討2017

    • Author(s)
      山崎文登、柴徳生、三谷幸代、林泰秀、市川仁
    • Organizer
      第59回日本小児血液・がん学会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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