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Leukemogenic pathway of TEL-AML1-positive leukemia

Research Project

Project/Area Number 26461587
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, 講師 (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, 准教授 (40420781)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords白血病 / 融合遺伝子 / TEL-AML1融合遺伝子 / 付加的遺伝子異常 / 小児血液学
Outline of Final Research Achievements

TEL-AML1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL). It alone is not enough to cause leukemia, and additional genetic change(s) are necessary. Retroviral vector-mediated insertional mutagenesis was applied on TEL-AML1-expressing hematopoietic progenitor cells to identify the cooperating genetic changes with TEL-AML1 in leukemogenesis. Tie2-positive cells containing immature hematopoietic progenitors were transduced by retroviral vector to induce insertional mutagenesis, and then transplanted into immunodeficient mice. In these mice B220-positive cells were expanded, and tumor formation was observed in some of them. Analysis of retroviral integration site in these tumors showed intra-genic insertion of viral sequences possibly resulting in disruption of gene expression/regulation. Genes located near the integration site may be the target of cooperating genetic changes necessary for leukemogenesis by TEL-AML1.

Report

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

    (28 results)

All 2016 2015 2014

All Journal Article (11 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] 遺伝子プロファイリングと癌治療 白血病2016

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

      癌と化学療法

      Volume: 43 Pages: 1341-1345

    • Related Report
      2016 Annual Research Report
  • [Journal Article] 小児白血病の発症過程 -白血病幹細胞とclonal evolution-2016

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

      日本臨牀

      Volume: 74(Suppl 8) Pages: 201-208

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Installation of multiple automated external defibrillators to prevent sudden death in school-aged children.2016

    • Author(s)
      Higaki T., Chisaka T, Moritani T, Ohta M, Takata H, Yamauchi T, Yamaguchi Y, Konishi K, Yamamoto E, Ochi F, Eguchi M, Eguchi-Ishimae M, Mitani Y, Ishii E
    • Journal Title

      Pediatr Int

      Volume: 58 Issue: 12 Pages: 1261-1265

    • DOI

      10.1111/ped.13143

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HMGA2 as a potential molecular target in KMT2A-AFF1-positive infant acute lymphoblastic leukaemia.2015

    • Author(s)
      Wu Z, Eguchi-Ishimae M, Yagi C, Iwabuki H, Gao W, Tauchi H, Inukai T, Sugita K, Ishii E, Eguchi M.
    • Journal Title

      Br J Haematol.

      Volume: 171 Issue: 5 Pages: 818-829

    • DOI

      10.1111/bjh.13763

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects2015

    • Author(s)
      Gao w, Eguchi M, et al.
    • Journal Title

      Human Genome Variation

      Volume: 2 Issue: 1 Pages: 15004-15004

    • DOI

      10.1038/hgv.2015.4

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of CD34+ and CD34- leukemia-initiating cells in MLL-rearranged human acute lymphoblastic leukemia2015

    • Author(s)
      Aoki Y, Eguchi M, et al.
    • Journal Title

      Blood

      Volume: 125 Issue: 6 Pages: 967-980

    • DOI

      10.1182/blood-2014-03-563304

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recent progress in leukemic stem cell research for childhood leukemia2015

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

      Rinsho Ketsueki

      Volume: 56 Issue: 10 Pages: 1871-1881

    • DOI

      10.11406/rinketsu.56.1871

    • NAID

      130005103302

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Installation of multiple AED to prevent sudden death in school-aged children.2015

    • Author(s)
      HIgaki T, Eguchi-Ishimae M, et al.
    • Journal Title

      Pediatric International

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lineage-dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia2014

    • Author(s)
      Tokuda K, Eguchi-Ishimae M, Iwabuki H, Kawakami S, Tauchi H, Ishii E, Eguchi M.
    • Journal Title

      Eur J Haematol

      Volume: 26(Epub ahead of print) Issue: 2 Pages: 177-181

    • DOI

      10.1111/ejh.12355

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] CLTC-ALK fusion as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm2014

    • Author(s)
      Tokuda K, Eguchi-Ishimae M, Yagi C, Kawabe M, Moritani K, Niiya T, Tauchi H, Ishii E, Eguchi M.
    • Journal Title

      Genes Chromosomes Cancer

      Volume: 53 Issue: 1 Pages: 78-89

    • DOI

      10.1002/gcc.22119

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] TEL-AML1型小児急性リンパ性白血病の分子学的機序2014

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

      血液内科

      Volume: 69 Pages: 644-651

    • Related Report
      2014 Research-status Report
  • [Presentation] 化学療法中に腸管穿孔を来した生体肝移植後バーキットリンパ腫の一例2016

    • Author(s)
      森谷京子、越智史博、米澤早知子、石前峰斉、江口真理子、田内久道、石井榮一、渋井勇一、山田耕治
    • Organizer
      第58回日本小児血液・がん学会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] 極端な偏食による巨赤芽球性貧血を発症した乳児の1例2016

    • Author(s)
      米澤早知子、森谷京子、石前峰斉、江口真理子、田内久道、石井榮一
    • Organizer
      第58回日本小児血液・がん学会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] MLL-AF4陽性急性リンパ性白血病の発症過程2016

    • Author(s)
      石前峰斉、江口真理子、田内久道、米澤早知子、森谷京子、石井榮一
    • Organizer
      第58回日本小児血液・がん学会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Impact of chromosome translocation in leukemia development2016

    • Author(s)
      江口真理子、石前峰斉、石井榮一
    • Organizer
      第78回日本血液学会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clonal evolution of CRLF2-rearranged ALL - Analysis of relapsed cases with P2RY8-CRLF2 fusion gene.2016

    • Author(s)
      石前峰斉、江口真理子、森谷京子、米澤早知子、手塚優子、田内久道、石井榮一
    • Organizer
      第78回日本血液学会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] HMGA2 as a potential molecular target in MLL-AF4 positive infant acute lymphoblastic leukemia.2016

    • Author(s)
      Eguchi M. Eguchi-Ishimae M, Wu Z, MingW, Iwabuki H, Tauchi H, Ishii E
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      京都市
    • Year and Date
      2016-04-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical application of next generation sequencing in a family with undiagnosed genetic conditions.2016

    • Author(s)
      Ozaki E, Eguchi-Ishimae M, Tezuka Y, Kagata K, Naruto T, Imoto I, Eguchi M, Ishii E
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      京都市
    • Year and Date
      2016-04-05
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FGFRLl is a possible candidate for the severe renal phenotype in a case of Wolf- Hirschhorn syndrome.2016

    • Author(s)
      Tezuka Y, Eguchi-Ishimae M, Ozaki E, Muriko K, Eguchi M, Ishii E
    • Organizer
      The13th International Congress of Human Genetics
    • Place of Presentation
      京都市
    • Year and Date
      2016-04-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 非寛解期に臍帯血移植を行った先天性急性単球生白血病の一例2015

    • Author(s)
      井上真依子、森谷京子、米澤早知子、江口真理子、石前峰斉、田内久道、石井榮一
    • Organizer
      第57回日本小児血液・がん学会
    • Place of Presentation
      山梨県甲府市
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
  • [Presentation] びまん性橋グリオーマ(DIPG)の治療経過中にサイトメガロウイルス感染から血球貪食症候群を発症した1剖検例2015

    • Author(s)
      久保田真理、田内久道、井上真依子、新田美里、森谷京子、米澤早知子、石前峰斉、江口真理子、石井榮一、倉田美恵、増本純也
    • Organizer
      第57回日本小児血液・がん学会
    • Place of Presentation
      山梨県甲府市
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 単一施設における小児がん患者の死亡例に関する検討2015

    • Author(s)
      米澤早知子、田内久道、新田美里、森谷京子、石前峰斉、江口真理子、石井榮一
    • Organizer
      第57回日本小児血液・がん学会
    • Place of Presentation
      山梨県甲府市
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Inafnt acute bilineal leukemia with MLL-AF4 fusion gene.2015

    • Author(s)
      石前峰斉、江口真理子、武洲英、森谷京子、米澤早知子、井上真依子、久保田真理、新田美里、手塚優子、田内久道、石井榮一
    • Organizer
      第77回日本血液学会
    • Place of Presentation
      石川県金沢市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] 当科で経験した小児がん経験者の二次がん4症例の検討2015

    • Author(s)
      新田美里、田内久道、米澤早知子、森谷京子、久保田真理、石前峰斉、江口真理子、石井榮一
    • Organizer
      第118回日本小児科学会
    • Place of Presentation
      大阪府大阪市
    • Year and Date
      2015-04-17
    • Related Report
      2015 Research-status Report
  • [Presentation] HMGA2 as a potential molecular target in MLL-AF4 positive infant acute lymphoblastic leukemia.2014

    • Author(s)
      石前峰斉、江口真理子ら
    • Organizer
      The 56th annual meeting of the American Society of Hematology
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 骨髄炎との鑑別が困難であった前駆B細胞性リンパ芽球型リンパ腫の一例2014

    • Author(s)
      森谷京子、石前峰斉ら
    • Organizer
      第56回日本小児血液・がん学会
    • Place of Presentation
      岡山
    • Year and Date
      2014-11-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 生後早期に発症したMLL-AF4陽性乳児急性骨髄性白血病の一例2014

    • Author(s)
      武洲英、石前峰斉ら
    • Organizer
      第56回日本小児血液・がん学会
    • Place of Presentation
      岡山
    • Year and Date
      2014-11-28
    • Related Report
      2014 Research-status Report
  • [Presentation] HMGA2阻害剤によるMLL-AF4陽性乳児急性リンパ性白血病細胞の増殖抑制効果2014

    • Author(s)
      石前峰斉、江口真理子ら
    • Organizer
      第76回日本血液学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31
    • Related Report
      2014 Research-status Report

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

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