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Development of a novel human leukemia model using humanized mice

Research Project

Project/Area Number 24659487
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

ISHII Naoto  東北大学, 医学(系)研究科(研究院), 教授 (60291267)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords白血病 / ヒト化マウス / 動物モデル / 白血病モデル / MLLキメラ遺伝子
Research Abstract

In vivo studies in which primary human leukemia cells were transplanted into immunodeficient mice, provided significant advances in our understanding of the pathogenesis of human leukemia. However, these models, in which the leukemia cells had already developed in human patients before being transplanted into mice, are not suitable for studying physiological leukemogenesis. Therefore, we here developed a new experimental model for analyzing leukemogenesis in which primary human HSCs are converted into leukemia cells by deliberate genetic hits. We hope that this newly established model using humanized mice will contribute to future studies aimed at revealing the molecular mechanisms for leukemogenesis and developing new therapies against leukemia.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report

Research Products

(31 results)

All 2014 2013 2012 Other

All Journal Article Presentation Remarks

  • [Journal Article] TNF receptor-associated factor 5 limits inflammatory CD4^+ T cell differentiation by antagonizing IL-6-receptor signaling2014

    • Author(s)
      Nagashima H, Okuyama Y, Asao A, Kawabe T, Yamaki S, Nakano H, Croft M, Ishii N, and So T
    • Journal Title

      Nat. Immunol.

      Volume: 15 Pages: 449-456

    • DOI

      10.1038/ni.2863

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Activation of Notch1 promotes development of human CD8^+ single positive T cells in humanized mice2014

    • Author(s)
      Haji Y, Suzuki M, Moriya K, So T, Hozumi K, Mizuma M, Unno M, and Ishii N.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 447 Pages: 346-351

    • DOI

      10.1016/j.bbrc.2014.04.003

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] OX40 ligand regulates splenic CD8(-) dendritic cell-induced Th2 responses in vivo.2014

    • Author(s)
      Kamachi F, Harada N, Usui Y, Sakanishi T, Ishii N, Okumura K, Miyake S, Akiba H
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 444 Pages: 235-240

    • DOI

      10.1016/j.bbrc.2014.01.060

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Hepatocyte growth factor regulated tyrosine kinase substrate in the peripheral development and function of B-cells2014

    • Author(s)
      Nagata T, Murata K, Murata R, Sun S-L, Saito Y, Yamaga S, Tanaka N, Tamai K, Moriya K, Kasai N, Sugamura K, and Ishii N.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 443 Pages: 351-356

    • DOI

      10.1016/j.bbrc.2013.11.029

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activation of Notch1 promotes development of human CD8+ single positive T cells in humanized mice2014

    • Author(s)
      Haji Y, Suzuki M, Moriya K, So T, Hozumi K, Mizuma M, Unno M, and Ishii N
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.2013

    • Author(s)
      Horino S, Uchiyama T, So T, Nagashima H, Sun SL, Sato M, Asao A, Haji Y, Sasahara Y, Candotti F, Tsuchiya S, Kure S, Sugamura K, and Ishii N
    • Journal Title

      PLos One

      Volume: 8

    • DOI

      10.1371/journal.pone.0071594

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Y chromosome-linked B and NK cell deficiency in mice.2013

    • Author(s)
      Sun SL, Horino S, Itoh-Nakadai A, Kawabe T, Asao A, Takahashi T, So T, Funayama R, Kondo M, Saitsu H, Matumoto N, Nakayama K, and Ishii N
    • Journal Title

      J. Immunol

      Volume: 190 Pages: 6209-6220

    • DOI

      10.4049/jimmunol.1300303

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Homeostatic proliferation of naïve CD4^+ T cells in mesenteric lymph nodes generates gut-tropic Th17 cells2013

    • Author(s)
      Kawabe T, Sun SL, Fujita T, Yamaki S, Asao A, Takahashi T, So T, Ishii N
    • Journal Title

      J. Immunol

      Volume: 190 Pages: 15788-5798

    • DOI

      10.4049/jimmunol.1203111

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A small molecule inhibitor to plasminogen activator inhibitor l inhibits macrophage migration.2013

    • Author(s)
      Ichimura A, Matsumoto S, Suzuki S, Dan T, Yamaki S, Sato Y, Kiyomoto H, Ishii N, Okada K, Matsuo O, Hou FF, Vaughan DE, van Ypersele de Strihou S, Miyata T.
    • Journal Title

      Arterioscler. Thromb. Vasc. Biol.

      Volume: 33 Pages: 935-42

    • DOI

      10.1161/atvbaha.113.301224

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential utility of eGFP-expressing NOG mice (NOG-EGFP) as a high purity cancer sampling system.2012

    • Author(s)
      Shima K, et al
    • Journal Title

      J. Exp Clin Cancer Res

      Volume: 31 Pages: 33-33

    • DOI

      10.1186/1756-9966-31-55

    • URL

      http://www.jeccr.com/content/31/1/55

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice.2012

    • Author(s)
      Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, and Ishii N.
    • Journal Title

      PLoS One

      Volume: 7(6)

    • DOI

      10.1371/journal.pone.0037892

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Runx1-deficiency in CD4^+ T cells causes fatal autoimmune inflammatory lung disease due to spontaneous hyperactivation of cells2012

    • Author(s)
      Wong WF, Tazawa R, (15名略)Nakata K, Takai T, Satake M.
    • Journal Title

      J. Immunol

      Volume: 188(11) Pages: 5408-20

    • DOI

      10.4049/jimmunol.1102991

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse.2012

    • Author(s)
      Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, Sugamura K.
    • Journal Title

      Int. Immunol

      Volume: 24 Pages: 208-214

    • DOI

      10.1093/intimm/dxs045

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Th17 cell generation and mucosal immunity2013

    • Author(s)
      Takeshi Kawabe, Shu-lan Sun, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, and Naoto Ishii
    • Organizer
      Annual International Symposium of Rheumatology Institute of Seoul National University Hospital
    • Place of Presentation
      Seoul
    • Year and Date
      2013-06-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Homeostatic proliferation of naïve CD4 T cells in mesenteric lymph nodes generates gut-tropic Th17 cells2013

    • Author(s)
      Takeshi Kawabe, Shu-lan Sun, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, and Naoto Ishii
    • Organizer
      The 1st Symposium of International Immunological Memory and Vaccine Forum
    • Place of Presentation
      東京
    • Year and Date
      2013-01-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Y chromosome-linked B and NK cell deficiency in mice2013

    • Author(s)
      Sun SL, Itoh A, Asao A, Takahashi T, So T, Kondo M, Ishii N.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Final Research Report
  • [Presentation] TRAF5 controls inflammatory CD4 T cells in experimental autoimmune encephalomyelitis2013

    • Author(s)
      Nagashima H, Yamaki S, Asao A, Croft M, Ishii N, So T.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉市
    • Related Report
      2013 Final Research Report
  • [Presentation] 腸管Th17細胞の産生における腸間膜リンパ節の役割2013

    • Author(s)
      河部剛史、孫舒嵐、鈴木信、山木聡史、浅尾敦子、宗孝紀、石井直人
    • Organizer
      第67回日本細菌学会東北支部総会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] TRAF5欠損マウスでは実験的自己免疫性脳脊髄炎が増悪する2013

    • Author(s)
      長島宏行、山木聡史、浅尾敦子、Michael Croft、石井直人、宗孝紀
    • Organizer
      第67回日本細菌学会東北支部総会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] Y-Chromosome-linked B- and NK-cell deficiency in mice2013

    • Author(s)
      Shu-lan Sun, Satoshi Horino, Ari Ito, Takeshi Kawabe, Atsuko Asao, Takeshi Takahashi, Takanori So, Motonari Kondo, and Naoto Ishii
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milano, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Homeostatic proliferation of naïve CD4 T cells in mesenteric lymph nodes generates gut-tropic Th17 cells2013

    • Author(s)
      Takeshi Kawabe, Shu-lan Sun, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, and Naoto Ishii
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      Milano, Italy
    • Related Report
      2013 Final Research Report
  • [Presentation] Homeostatic proliferation of naïve CD4 T cells in mesenteric lymph nodes generates gut-tropic Th17 cells2013

    • Author(s)
      Takeshi Kawabe, Shu-lan Sun, Satoshi Yamaki, Atsuko Asao, Takeshi Takahashi, Takanori So, and Naoto Ishii
    • Organizer
      NIH-Tohoku University-JSPS Symposium
    • Place of Presentation
      Sendai
    • Related Report
      2013 Final Research Report
  • [Presentation] Homeostatic proliferation occurs in mesenteric lymph nodes generates gut-tropic Th17 cells.2013

    • Author(s)
      Takeshi Kawabe et al.
    • Organizer
      The 1st Symposium of International Immunological Memory and Vaccine Forum
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] TNF receptor-associated factor 5 inhibits Th17 and Tfh differentiation2012

    • Author(s)
      Nagashima H, Yamaki S, Croft M, Ishii N, So T.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] Homeostatic proliferation occurs in mesenteric lymph nodes and supplies effector memory CD4^+ T cells in the intestine2012

    • Author(s)
      Kawabe T, Sun SL, Yamaki S, Asao A, Takahashi T, So T, Ishii N.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Final Research Report
  • [Presentation] L-arginine upregulates NO production by macrophages during infection with Leishmania major2012

    • Author(s)
      Asao A, So T, Hoshino T, Asao H, Sugmura K, Ishii N.
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2013 Final Research Report
  • [Presentation] リーシュマニア原虫感染防御におけるL-アルギニンの効果2012

    • Author(s)
      浅尾敦子、宗孝紀、Lishomwa C. Ndhlovu、浅尾裕信、菅村和夫、石井直人
    • Organizer
      第66回日本細菌学会東北支部総会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] TNF receptor-associated factor 5によるヘルパーT細胞制御機構の解明2012

    • Author(s)
      長島宏行、山木聡史、Michael Croft、石井直人、宗孝紀
    • Organizer
      第66回日本細菌学会東北支部総会
    • Place of Presentation
      仙台市
    • Related Report
      2013 Final Research Report
  • [Presentation] L-arginine upregulates NO production by macrophages during infection with Leishmania major.2012

    • Author(s)
      Atsuko Asaoほか
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2012 Research-status Report
  • [Presentation] Homeostatic proliferation occurs in mesenteric lymph nodes and supplies effector memory CD4+ T cells in the intestine.2012

    • Author(s)
      Takeshi Kawabeほか
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸市
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.immunol.med.tohoku.ac.jp//index.html

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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