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Process of in utero leukemogenic fusion gene generation in childhood acute leukemia

Research Project

Project/Area Number 19K08866
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionEhime University

Principal Investigator

EGUCHI MARIKO  愛媛大学, 医学系研究科, 教授 (40420781)

Co-Investigator(Kenkyū-buntansha) 江口 峰斉  愛媛大学, 医学部附属病院, 准教授 (50420782)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords白血病 / MLL融合遺伝子 / 遺伝的背景 / iPS細胞 / 白血病幹細胞 / 小児 / 遺伝子異常
Outline of Research at the Start

急性白血病は小児期で最も多いがんである。抗がん剤の多剤併用による化学療法の発展により、その治療成績は改善したが、化学療法によって障害を残し、治癒後長期にわたり後遺障害に苦しむ患者も少なくない。近年分子標的療法として、白血病特異的な遺伝子異常をターゲットとした治療法が開発・応用されているが、白血病の後遺症なき根治のための戦略として有効な方法は分子標的療法に加えて、その発症予防および再発予防である。本研究では、小児急性白血病の発症に至るプロセス、特に白血病幹細胞の成立に必須な遺伝子異常の獲得プロセスを解明し、小児急性白血病の発症および再発予防の可能性について検討することを目的とする。

Outline of Final Research Achievements

To clarify the process leading to generation of MLL fusion gene in utero, hematopoietic cell differentiation using patient-derived iPS cells were analyzed. iPS cells were established from the peripheral blood of three patients with MLL fusion gene-positive leukemia in remission as well as from three healthy adults. Established iPS cells were differentiated into CD34-positive hematopoietic progenitor cells and further differentiated into B lymphocyte progenitor cells. During the process of hematopoietic differentiation, generation of MLL fusion gene was examined by the inverse PCR method. Hematopoietic progenitor cells obtained from all three patient-derived iPS cells harbored MLL fusion gene in low frequency, which was not detected in iPS from healthy controls. Formation of MLL fusion gene did not depend on the addition of TopoII inhibitor. It was suggested that some, yet unknown genetic background of the patient may be involved in the generation of the MLL fusion gene.

Academic Significance and Societal Importance of the Research Achievements

MLL融合遺伝子を有する乳児急性リンパ性白血病は、予後の改善が著しい小児白血病の中で、今なお治療抵抗性の白血病である。MLL融合遺伝子陽性乳児白血病の発症過程を明らかにし、発症予防につながる情報を得るため、患者細胞より樹立したiPS細胞を用いた造血細胞への分化系を確立し、白血病発症の初期段階のMLL融合遺伝子の形成のメカニズムについて検討した。その結果MLL融合遺伝子の形成には患者が有する何らかの要因(遺伝的背景など)が関与している可能性が示唆された。この遺伝的背景と、関与しうる環境要因などの外的因子を明らかにすることにより、MLL融合遺伝子陽性の乳児白血病の発症予防につながる可能性がある。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (33 results)

All 2021 2020 2019

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 9 results) Presentation (15 results) (of which Invited: 4 results) Book (2 results)

  • [Journal Article] Acute leukemia of infants and neonates2021

    • Author(s)
      江口真理子
    • Journal Title

      Rinsho Ketsueki

      Volume: 62 Issue: 8 Pages: 1308-1318

    • DOI

      10.11406/rinketsu.62.1308

    • NAID

      130008085945

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2021 Annual Research Report
  • [Journal Article] Leukemogenic pathway of infant leukemia with <i>MLL</i> fusion2021

    • Author(s)
      江口真理子
    • Journal Title

      Rinsho Ketsueki

      Volume: 62 Issue: 7 Pages: 809-819

    • DOI

      10.11406/rinketsu.62.809

    • NAID

      130008071861

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia2021

    • Author(s)
      de Groot AP.、Saito Y、Kawakami E、Hashimoto M、Aoki Y、Ono R、Ogahara I、Fujiki S、Kaneko A、Sato K、Kajita H、Watanabe T、Takagi M、Tomizawa D、Koh K、Eguchi M、Ishii Ei、Ohara O、Shultz LD.、Mizutani S、Ishikawa F
    • Journal Title

      EBioMedicine

      Volume: 64 Pages: 103235-103235

    • DOI

      10.1016/j.ebiom.2021.103235

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Noninvasive ultrasound technique for assessment of liver fibrosis and cardiac function in Fontan-associated liver disease: diagnosis based on elastography and hepatic vein waveform type2021

    • Author(s)
      Koizumi Yohei、Hirooka Masashi、Tanaka Takaaki、Watanabe Takao、Yoshida Osamu、Tokumoto Yoshio、Higaki Takashi、Eguchi Mariko、Abe Masanori、Hiasa Yoichi
    • Journal Title

      Journal of Medical Ultrasonics

      Volume: 48 Issue: 2 Pages: 235-244

    • DOI

      10.1007/s10396-020-01078-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metaplastic carcinoma of the breast and BRCA1 germline mutation: a case report and review2021

    • Author(s)
      Yamashita Michiko、Kamei Yoshiaki、Murakami Akari、Ozaki Erina、Okujima Kumiko、Takemoto Kana、Takaoka Megumi、Tsukamoto Daiki、Kusakabe Erina、Shidahara Tomoyuki、Noda Haruna、Aoki Reina、Taguchi Kana、Nishiyama Kanako、Eguchi Mariko、Takada Yasutsugu
    • Journal Title

      Hereditary Cancer in Clinical Practice

      Volume: 19 Issue: 1 Pages: 3-3

    • DOI

      10.1186/s13053-020-00162-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel SOX10 variant in a Japanese girl with Waardenburg syndrome type 4C and Kallmann syndrome2020

    • Author(s)
      Hamada Junpei、Ochi Fumihiro、Sei Yuka、Takemoto Koji、Hirai Hiroki、Honda Misa、Shibata Hironori、Hasegawa Tomonobu、Eguchi Mariko
    • Journal Title

      Human Genome Variation

      Volume: 7 Issue: 1 Pages: 30-30

    • DOI

      10.1038/s41439-020-00118-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lister hooded rats as a novel animal model of attention-deficit/hyperactivity disorder2020

    • Author(s)
      Jogamoto Toshihiro、Utsunomiya Ryo、Sato Arisa、Kihara Nanako、Choudhury Mohammed E.、Miyanishi Kazuya、Kubo Madoka、Nagai Masahiro、Nomoto Masahiro、Yano Hajime、Shimizu Yusuke I.、Fukuda Mitsumasa、Ishii Eiichi、Eguchi Mariko、Tanaka Junya
    • Journal Title

      Neurochemistry International

      Volume: 141 Pages: 104857-104857

    • DOI

      10.1016/j.neuint.2020.104857

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of Human CBF1-Targeting Single-Stranded DNA Aptamers with Antiangiogenic Activity In Vitro2020

    • Author(s)
      Tezuka-Kagajo Mari、Maekawa Masashi、Ogawa Atsushi、Hatta Yoshiko、Ishii Eiichi、Eguchi Mariko、Higashiyama Shigeki
    • Journal Title

      Nucleic Acid Therapeutics

      Volume: 30 Issue: 6 Pages: 365-378

    • DOI

      10.1089/nat.2020.0875

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survey of patients with spinal muscular atrophy on the island of Shikoku, Japan2020

    • Author(s)
      Okamoto K、Motoki T、Saito I、Urate R、Aibara K、Jogamoto T、Fukuda M、Wakamoto H、Maniwa S、Kondo Y、Toda Y、Goji A、Mori T、Soga T、Konishi Y、Nagai S、Takami Y、Tokorodani C、Nishiuchi R、Usui D、Ando R、Tada S、Yamanishi Y、Nagai M、Arakawa R、Saito K、Nishio H、Ishii E、Eguchi M
    • Journal Title

      Brain and Development

      Volume: 42 Issue: 8 Pages: 594-602

    • DOI

      10.1016/j.braindev.2020.05.004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renal dysfunction can occur in advanced-stage Duchenne muscular dystrophy.2020

    • Author(s)
      Motoki T, Shimizu-Motohashi Y, Saito I, Komaki H, Ishiyama A, Aibara K, Jogamoto T, Tezuka Y, Kawabe M, Makino A, Nagatani K, Tatara K, Kuwabara K, Kikuchi C, Fukuda M, Ishii E, Eguchi M
    • Journal Title

      Muscle and Nerve

      Volume: 61 Issue: 2 Pages: 192-197

    • DOI

      10.1002/mus.26757

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonocclusive Mesenteric Ischemia Rescued by Immediate Surgical Exploration in a Boy with Severe Neurodevelopmental Disability.2019

    • Author(s)
      Mizumoto M, Ochi F, Jogamoto T, Okamoto K, Fukuda M, Yamauchi T, Miyata T, Tashiro R, Eguchi M, Kitazawa R, Ishii E
    • Journal Title

      Case Reports in Pediatrics

      Volume: 2019 Pages: 1-4

    • DOI

      10.1155/2019/5354074

    • Related Report
      2019 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Early Surgery Is Feasible for a Very Large Congenital Infantile Fibrosarcoma Associated With Life Threatening Coagulopathy: A Case Report and Literature Review.2019

    • Author(s)
      Alias H, Abdul Rashid AH, Lau SCD, Loh C-K, Sapuan J, Ibrahim S, Md Zin RR, Chow YP, Kanegane H, Eguchi M
    • Journal Title

      Frontiers in Pediatrics

      Volume: 7 Pages: 529-529

    • DOI

      10.3389/fped.2019.00529

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 乳児・新生児白血病のゲノム異常2021

    • Author(s)
      江口真理子
    • Organizer
      第83回日本血液学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 小児白血病のゲノム異常2020

    • Author(s)
      江口真理子
    • Organizer
      第72回中国四国小児科学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 乳児白血病2020

    • Author(s)
      江口真理子
    • Organizer
      JCF2020(ジャパンキャンサーフォーラム)
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 乳児白血病の発症過程2020

    • Author(s)
      江口真理子
    • Organizer
      第82回日本血液学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] モザイクを示唆するゲノムコピー数増加のデータをきっかけに確認した染色体異数性異常/構造異常のモザイク症例の検証と考察2020

    • Author(s)
      涌井慶子、髙野亨子、水野誠司、江口真理子、松田和之、重藤翔平、根岸達哉、山口智美、古庄知己、福嶋義光
    • Organizer
      日本人類遺伝学会第65回大会
    • Related Report
      2020 Research-status Report
  • [Presentation] paternal uniparental disomy(patUPD)モザイクを示したBeckwith-Wiedemann症候群に合併した肝芽腫の1例2020

    • Author(s)
      18.宮脇零士、岩本麻友美、加賀城真理、森谷京子、石前峰斉、田内久道、江口真理子、永井功造、東元 健、副島英伸
    • Organizer
      第62回小児血液がん学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Development of human CBF1-targeting single-stranded DNA aptamers as angiogenic inhibitors.2020

    • Author(s)
      20.Tezuka-Kagajo M, Hatta Y, Maekawa M, Ogawa A, Ishimae M, Eguchi M, Higashiyama S
    • Organizer
      第79回日本癌学会学術集会
    • Related Report
      2020 Research-status Report
  • [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 Research-status Report
  • [Presentation] Li-Fraumeni症候群の遺伝学的検査とその意義2019

    • Author(s)
      加藤芙美乃、木戸滋子、尾崎依里奈、江口真理子、西久保敏也、冨田尚裕、田村和朗
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Research-status 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 Research-status Report
  • [Presentation] 当院における 6年間の無侵襲的出生前遺伝学的検査 (NIPT) 外来受診妊婦の検討2019

    • Author(s)
      松原裕子、松原圭一、内倉友香、高木香津子、杉山隆、江口真理子
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Research-status 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 Research-status 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 Research-status 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 Research-status 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 Research-status Report
  • [Book] 今日の治療指針2021年版 血球貪食性リンパ組織球症、血球貪食症候群2021

    • Author(s)
      江口真理子(分担)
    • Total Pages
      2000
    • Publisher
      医学書院
    • ISBN
      9784260042826
    • Related Report
      2020 Research-status Report
  • [Book] ヘマトロジー3 -悪性リンパ腫に対する新たな治療展開ー トピックス AYA世代の造血器腫瘍の遺伝子異常と治療戦略2020

    • Author(s)
      江口真理子
    • Total Pages
      112
    • Publisher
      クリニコ出版
    • ISBN
      9784910396040
    • Related Report
      2020 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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