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Tests for self-renewal signals of acute leukemia stem cells and prediction of the effects of molecular-targeted drugs for the signals

Research Project

Project/Area Number 26460669
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Laboratory medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

TOHDA Shuji  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80251510)

Research Collaborator OHTAKA Mika  東京医科歯科大学, 大学院医歯学総合研究科
SHIRATORI Erika  東京医科歯科大学, 大学院医歯学総合研究科
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords白血病 / 白血病幹細胞 / 分子標的薬 / 薬剤感受性検査 / 幹細胞 / NOTCH / BMI1 / MYD88 / 自己複製
Outline of Final Research Achievements

To cure acute leukemia, development of two tests is required: tests to identify the signals regulating stemness of leukemia stem cells and sensitivity tests of the molecular-targeted drugs for the signals. We have found that BMI1 signal and NOTCH signal regulate the stemness of leukemia stem cells using in vitro culture assay. We also showed that the inhibitors suppressed the cell growth and stemness-related signaling. These findings indicate the possibility that the inhibitors can be molecular-targeted drugs. We also developed the drug-sensitivity tests.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 2014 Other

All Journal Article (6 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Book (3 results) Remarks (1 results)

  • [Journal Article] Detection of the MYD88 mutation by the combination of the allele-specific PCR and quenching probe methods2017

    • Author(s)
      Nogami S, Kawaguchi-Ihara N, Shiratori E, Ohtaka M, Itoh M, Tohda S
    • Journal Title

      International Journal of Laboratory Hematology

      Volume: 39 Issue: 2 Pages: 163-168

    • DOI

      10.1111/ijlh.12598

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 腫瘍マーカーとコンパニオン診断の適切利用による個別化医療の推進2017

    • Author(s)
      東田修二
    • Journal Title

      臨床病理

      Volume: 65 Pages: 314-316

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Establishment of a quenching probe method for detection of NPM1 mutations in acute myeloid leukemia cells2016

    • Author(s)
      Kawaguchi-Ihara N, Itoh M, Murohashi I, Tohda S
    • Journal Title

      Oncology Letters

      Volume: 4 Pages: 2429-2432

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 造血器腫瘍のバイオマーカー:白血病幹細胞の個性診断をめざして2015

    • Author(s)
      東田修二
    • Journal Title

      臨床病理

      Volume: 63 Pages: 1110-1113

    • Related Report
      2015 Research-status Report
  • [Journal Article] NOTCH signaling roles in acute myeloid leukemia cell growth and interaction with other stemness-related signals2014

    • Author(s)
      Tohda S
    • Journal Title

      Anticancer Research

      Volume: 34 Pages: 6259-6264

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of EPH-ephrin signaling on the growth of human leukemia cells2014

    • Author(s)
      Takahashi Y, Itoh M, Nara N, Tohda S
    • Journal Title

      Anticancer Research

      Volume: 34 Pages: 2913-2918

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Mechanisms of suppressive effects of MYD88 Inhibitors on the Growth of Lymphoma and Leukemia Cells2016

    • Author(s)
      Erika Shiratori, Mai Itoh, Mika Ohtaka, Shohei Nogami, Shuji Tohda
    • Organizer
      The 58th American Society of Hematology
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2016-12-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MYD88の阻害によるリンパ腫細胞の増殖抑制作用2016

    • Author(s)
      白鳥恵理香、野上祥平、大高美香、伊藤真以、東田修二
    • Organizer
      第63回日本臨床検査医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 白血病細胞でのNOTCHシグナル活性化に伴うmicroRNA発現の変化2016

    • Author(s)
      野上祥平、白鳥恵理香、大高美香、伊藤真以、東田修二
    • Organizer
      第63回日本臨床検査医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] BMI1 阻害剤による白血病細胞のアポトーシス誘導を介した増殖抑制作用2016

    • Author(s)
      大高美香、野上祥平、白鳥恵理香、伊藤真以、東田修二
    • Organizer
      第63回日本臨床検査医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 急性Tリンパ芽球性白血病におけるPTENの機能解析2016

    • Author(s)
      奥橋佑基、細萓茂実、東田修二
    • Organizer
      第63回日本臨床検査医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2016-09-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腫瘍マーカーとコンパニオン診断の適切利用による個別化医療の推進2016

    • Author(s)
      東田修二
    • Organizer
      第63回日本臨床検査医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2016-09-03
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 白血病細胞の増殖に対するMERチロシンキナーゼの阻害剤の作用2016

    • Author(s)
      甲田祐樹、大高美香、白鳥恵理香、伊藤真以、東田修二
    • Organizer
      第63回日本臨床検査医学会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2016-09-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Highly Sensitive Detection of MYD88 Mutation by Combination of Allele-specific PCR and Quenching Probe Method2016

    • Author(s)
      Shohei Nogami, Mai Itoh, and Shuji Tohda
    • Organizer
      The 14th Asian Society for Clinical Pathology and Laboratory Medicine Congress
    • Place of Presentation
      National Taiwan University (Taipei, Taiwan)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] リンパ腫・白血病細胞株の増殖に対するMYD88阻害薬とBTK阻害薬の作用2015

    • Author(s)
      白鳥恵理香、野上祥平、王詩淳、大高美香、伊藤真以、東田修二
    • Organizer
      第62回日本臨床検査医学会学術集会
    • Place of Presentation
      長良川国際会議場(岐阜市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 白血病細胞における糖転移酵素の発現とNotchシグナル活性化との関連2015

    • Author(s)
      王詩淳、野上祥平、白鳥恵理香、大高美香、伊藤真以、東田修二
    • Organizer
      第62回日本臨床検査医学会学術集会
    • Place of Presentation
      長良川国際会議場(岐阜市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 白血病細胞に対するBMI阻害剤の細胞分子生物学的作用2015

    • Author(s)
      大高美香、白鳥恵理香、王詩淳、野上祥平、伊藤真以、東田修二
    • Organizer
      第62回日本臨床検査医学会学術集会
    • Place of Presentation
      長良川国際会議場(岐阜市)
    • Year and Date
      2015-11-20
    • Related Report
      2015 Research-status Report
  • [Presentation] Effects of GLI1 and CTNNB1 knockdown on NOTCH signaling of leukemia cells2014

    • Author(s)
      Yuki Okuhashi, Yusuke Takahashi, Mika Ohtaka, Erika Shiratori, Shijun O, Mai Itoh, Shuji Tohda
    • Organizer
      The 56th American Society of Hematology
    • Place of Presentation
      サンフランシスコ(アメリカ)
    • Year and Date
      2014-12-06
    • Related Report
      2014 Research-status Report
  • [Presentation] 造血器腫瘍のバイオマーカー:白血病幹細胞の個性診断をめざして. シンポジウム 癌生物学とバイオマーカー探索2014

    • Author(s)
      東田修二
    • Organizer
      第61回日本臨床検査医学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-11-25
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 白血病細胞の増殖に対するBmi1阻害剤の作用2014

    • Author(s)
      大高美香、高橋祐介、白鳥恵理香、伊藤真以、東田修二
    • Organizer
      第61回日本臨床検査医学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-11-24
    • Related Report
      2014 Research-status Report
  • [Presentation] BCR-ABL融合遺伝子の定量RT-PCR法と定性RT-Nested PCR法での検出感度の比較2014

    • Author(s)
      白鳥恵理香、大高美香、高橋祐介、伊藤真以、東田修二
    • Organizer
      第61回日本臨床検査医学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-11-24
    • Related Report
      2014 Research-status Report
  • [Presentation] Quenching probe法を用いたNPM1遺伝子変異の検出法2014

    • Author(s)
      川口寛子、伊藤真以、室橋郁生、東田修二
    • Organizer
      第61回日本臨床検査医学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2014-11-24
    • Related Report
      2014 Research-status Report
  • [Book] 日常診療のための検査値のみかた - 造血器腫瘍関連染色体・遺伝子検査2015

    • Author(s)
      東田修二(分担執筆)
    • Total Pages
      757
    • Publisher
      中外医学社
    • Related Report
      2015 Research-status Report
  • [Book] 臨床検査のガイドラインJSLM20152015

    • Author(s)
      東田修二(分担執筆)
    • Total Pages
      446
    • Publisher
      日本臨床検査医学会
    • Related Report
      2015 Research-status Report
  • [Book] 遺伝子・染色体検査学2015

    • Author(s)
      池内達郎、小原深美子、東田修二、中田章史、奈良信雄、吉田光明
    • Total Pages
      244
    • Publisher
      医歯薬出版
    • Related Report
      2014 Research-status Report
  • [Remarks] 東京医科歯科大学 臨床検査医学

    • URL

      http://www.tmd.ac.jp/med/mlab/mlab-J.html

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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