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Characterization of pre-leukemic stem cells in childhood acute lymphoblastic leukemia

Research Project

Project/Area Number 17K10115
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionEhime University

Principal Investigator

Eguchi-Ishimae Minenori  愛媛大学, 医学部附属病院, 准教授 (50420782)

Co-Investigator(Kenkyū-buntansha) 石井 榮一  愛媛大学, 医学系研究科, 教授 (20176126)
江口 真理子  愛媛大学, 医学系研究科, 教授 (40420781)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords小児白血病 / 白血病幹細胞 / 前白血病幹細胞 / MLL-AF4融合遺伝子 / TEL-AML1融合遺伝子 / MLL融合遺伝子 / TEL融合遺伝子 / 小児血液学 / 白血病
Outline of Final Research Achievements

MLL-AF4 and TEL-AML1 fusion genes are frequently observed in childhood acute lymphocytic leukemia (ALL). Leukemogenic process with these fusion genes were analyzed in vitro and in vivo with mouse embryonic stem (ES) cell expressing MLL-AF4 or TEL-AML1 fusion and immunodeficient mice (NOG mice) transplanted with fusion gene-expressing ES cell-derived immature hematopoietic cells. It was shown that the presence of these leukemia-specific fusion genes alone was not sufficient for leukemic transformation and hematopoietic progenitors with MLL-AF4 or TEL-AML1 fusion still remained at the stage of pre-leukemic stem cell without full transformation activity to cause leukemia rapidly in immunodeficient mice. These pre-leukemic stem cells could progress to leukemic stem cell after introducing random insertional mutations by retroviral integration indicating that some additional genetic abnormalities may be essential for the final progression to leukemic stem cells and leukemic transformation.

Academic Significance and Societal Importance of the Research Achievements

白血病における前白血病幹細胞の存在は以前から示唆されてきたが、小児白血病における詳細な研究は少ない。前白血病幹細胞は多様な白血病幹細胞を生み出す発生母地となり、白血病再発・治療抵抗性の原因となり得る細胞であるが、現在まで治療対象としての研究もなされていない。白血病の再発の連鎖を断ち切るためには前白血病幹細胞の根絶が必須であり、その生存・維持のメカニズムと白血病幹細胞への進展のメカニズムが明らかになれば、新たな分子標的療法の開発へつながり、小児のみならず、成人領域の白血病患者の予後改善が可能となる。

Report

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

    (28 results)

All 2020 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 3 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Brain Abscess Associated with Polymicrobial Infection after Intraoral Laceration: A Pediatric Case Report.2020

    • Author(s)
      Ochi F, Tauchi H, Miyata T, Moritani T, Chisaka T, Hamada J, Nagai K, Eguchi-Ishimae M, Eguchi M
    • Journal Title

      Case Reports in Pediatrics

      Volume: 2020 Pages: 1-5

    • DOI

      10.1155/2020/8304302

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集小児のがん-最近の動向 1.白血病2019

    • Author(s)
      江口真理子, 石前峰斉, 石井榮一
    • Journal Title

      小児科

      Volume: 60 Pages: 1009-1020

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Mesenchymal Stem Cell Therapy Overcomes Steroid Resistance in Severe Gastrointestinal Acute Graft-Versus-Host Disease.2019

    • Author(s)
      Moritani K, Miyawaki R, Tokuda K, Ochi F, Eguchi-Ishimae M, Tauchi H, Eguchi M, Ishii E, Nagai K
    • Journal Title

      Case Rep Transplant

      Volume: 2019 Pages: 1-5

    • DOI

      10.1155/2019/7890673

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early detection of the PAX3-FOXO1 fusion gene in circulating tumor-derived DNA in a case of alveolar rhabdomyosarcoma2019

    • Author(s)
      Eguchi-Ishimae M, Tezuka M, Kokeguchi T, Nagai K, Moritani K, Yonezawa S, Tauchi H, Tokuda K, Ishida Y, Ishii E, Eguchi M
    • Journal Title

      Genes Chromosomes Cancer

      Volume: 印刷中 Issue: 8 Pages: 521-529

    • DOI

      10.1002/gcc.22734

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prolonged adrenal insufficiency after high-dose glucocorticoid in infants with leukemia.2018

    • Author(s)
      Moritani K, Nagai K, Ochi F, Yonezawa S, Takemoto K, Tokuda K, Tauchi H, Eguchi-Ishimae M, Eguchi M, Ishii E
    • Journal Title

      Pediatric Hematology and Oncology

      Volume: 35 Issue: 5-6 Pages: 355-361

    • DOI

      10.1080/08880018.2018.1539148

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Usefulness of positron emission tomography-CT for diagnosis of primary bone marrow lymphoma in children.2018

    • Author(s)
      Moritani K, Nakano N, Yonezawa S, Ochi F, Tauchi H, Eguchi-Ishimae M, Eguchi M, Ishii E, Nagai K
    • Journal Title

      Pediatric Hematology and Oncology

      Volume: 35 Pages: 125-130

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Exon skipping in CYBB mRNA and skewed inactivation of X chromosome cause late-onset chronic granulomatous disease2018

    • Author(s)
      Eguchi M、Yagi C、Tauchi H、Kobayashi M、Ishii E、Eguchi-Ishimae M
    • Journal Title

      Pediatric Hematology and Oncology

      Volume: 35 Issue: 5-6 Pages: 341-349

    • DOI

      10.1080/08880018.2018.1522402

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Manifestation of recessive combined D-2-, L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome2018

    • Author(s)
      Eguchi Mariko、Ozaki Erina、Yamauchi Toshifumi、Ohta Masaaki、Higaki Takashi、Masuda Kiyoshi、Imoto Issei、Ishii Eiichi、Eguchi-Ishimae Minenori
    • Journal Title

      American Journal of Medical Genetics Part A

      Volume: 176 Issue: 2 Pages: 351-358

    • DOI

      10.1002/ajmg.a.38578

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 乳児白血病の病態解明と治療研究の変遷2018

    • Author(s)
      石井榮一、江口真理子、石前峰斉
    • Journal Title

      日本小児血液・がん学会雑誌

      Volume: 55 Pages: 345-351

    • NAID

      130007580478

    • Related Report
      2018 Research-status Report
  • [Journal Article] ゲノム研究の臨床応用-小児科学講座における取り組み-2018

    • Author(s)
      江口真理子、石前峰斉、石井榮一
    • Journal Title

      愛媛医学

      Volume: 37 Pages: 124-130

    • Related Report
      2018 Research-status Report
  • [Journal Article] Histological characterisation of visceral changes in a patient with type 2 Gaucher disease treated with enzyme replacement therapy2018

    • Author(s)
      Tezuka Yuko、Fukuda Mitsumasa、Watanabe Shohei、Nakano Takeshi、Okamoto Kentaro、Kuzume Kazuyo、Yano Yoshiaki、Eguchi Mariko、Ishimae Minenori、Ishii Eiichi、Miyazaki Tatsuhiko
    • Journal Title

      Blood Cells, Molecules, and Diseases

      Volume: 68 Pages: 194-199

    • DOI

      10.1016/j.bcmd.2016.11.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Usefulness of positron emission tomography-CT for diagnosis of primary bone marrow lymphoma in children2018

    • Author(s)
      Moritani Kyoko、Nakano Naoko、Yonezawa Sachiko、Ochi Fumihiro、Tauchi Hisamichi、Eguchi-Ishimae Minenori、Eguchi Mariko、Ishii Eiichi、Nagai Kozo
    • Journal Title

      Pediatric Hematology and Oncology

      Volume: 印刷中 Issue: 2 Pages: 125-130

    • DOI

      10.1080/08880018.2018.1459984

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 愛媛県における希少・未診断例の現状調査2019

    • Author(s)
      尾崎依里奈、石前峰斉、江口真理子
    • Organizer
      第26回日本遺伝子診療学会大会 第43回日本遺伝カウンセリング学会学術集会合同学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 四国四県における希少・未診断例の現状調査2019

    • Author(s)
      尾崎依里奈、石前峰斉、江口真理子
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 男性化徴候とCushing徴候を契機に発見された悪性卵巣ステロイド産生腫瘍の4歳女児例2019

    • Author(s)
      永井功造、宮脇零士、森谷京子、手束真理、桑原淳、大久保一宏、竜田恭介、石前峰斉、田内久道、江口真理子
    • Organizer
      第61回日本小児血液・がん学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 慢性骨髄性白血病の初期治療としてニロチニブを使用した2症例2019

    • Author(s)
      森谷京子、宮脇零士、手束真理、永井功造、石前峰斉、田内久道、江口真理子
    • Organizer
      第61回日本小児血液・がん学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 小児急性リンパ性白血病におけるDUX4-IGH融合遺伝子の迅速な同定2019

    • Author(s)
      石前峰斉、森谷京子、永井功造、宮脇零士、米澤早知子、宮本真知子、手束真理、田内久道、石井榮一、江口真理子
    • Organizer
      第61回日本小児血液・がん学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 歩行障害、動作時振戦から発見された腫瘍随伴神経症候群を伴った神経芽腫の1例2019

    • Author(s)
      宮脇零士、永井功造、森谷京子、手束真理、元木崇裕、桑原淳、竜田恭介、石前峰斉、田内久道、江口真理子
    • Organizer
      第61回日本小児血液・がん学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Leukemogenic pathway of MLL-AF4 fusion-positive acute lymphoblastic leukemia.2018

    • Author(s)
      Eguchi M, Eguchi-Ishimae M, Iwabuki H, Ishii E
    • Organizer
      Global Summit on Hematologic Malignancies
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院における小児固形腫瘍4例に使用した末梢血幹細胞採取におけるプレリキサホルの有効性と安全性について2018

    • Author(s)
      永井功造、森谷京子、手束真理、田内久道、石前峰斉、江口真理子、石井榮一
    • Organizer
      第60回日本小児血液がん学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 小児急性リンパ性白血病におけるFGFR1の高発現2018

    • Author(s)
      江口真理子、石前峰斉、森谷京子、永井功造、米澤早知子、手束真理、田内久道、石井榮一
    • Organizer
      第80回日本血液学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 網羅的遺伝子解析により診断したD-2-hydroxyglutaric aciduriaとIDH2変異によるTリンパ球のクローナルな増殖2018

    • Author(s)
      江口真理子、相原香織、尾崎依里奈、村尾紀久子、中野直子、高田秀実、石前峰斉、石井榮一
    • Organizer
      第63回日本人類遺伝学会
    • Related Report
      2018 Research-status Report
  • [Presentation] MLL-AF4転座型急性リンパ性白血における付加的遺伝子異常の意義2018

    • Author(s)
      江口真理子、石前峰斉
    • Organizer
      第77回日本癌学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Fn14(Fibroblast growth factor-inducible 14)はIgA腎症において、糸球体病変形成の早期から関与している2018

    • Author(s)
      手塚優子、石前峰斉、尾崎依里奈、伊藤敏恭、石井榮一、江口真理子
    • Organizer
      第53回日本小児腎臓病学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Leukemogenic pathway of MLL-AF4 fusion-positive acute lymphoblastic leukemia.2017

    • Author(s)
      Eguchi M. Eeuchi-Ishimae M. Ishii E
    • Organizer
      59th Annual meeting of the American Society of Hematology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 小児期発症の遺伝性腫瘍に対するゲノム情報の取り扱いとその課題2017

    • Author(s)
      江口真理子
    • Organizer
      第59回日本小児血液・がん学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 血漿腫瘍由来DNAを用いた横紋筋肉腫の検出とフォローアップ2017

    • Author(s)
      石前峰斉、江口真理子、田内久道、米澤早知子、森谷京子、永井功造、石井榮一、苔口知樹、徳田桐子、石田也寸志
    • Organizer
      第59回日本小児血液・がん学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Manifestation of recessive combined D-2-,L-2-hydroxyglutaric aciduria in combination with 22q11.2 deletion syndrome.2017

    • Author(s)
      江口真理子、尾崎依里奈、山内俊史、太田雅明、檜垣高史、石井榮一、石前峰斉ら
    • Organizer
      第62回日本人類遺伝学会
    • Related Report
      2017 Research-status Report

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

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