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The role of Notch signaling in the leukemia stem cells.

Research Project

Project/Area Number 20591111
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionThe University of Tokyo

Principal Investigator

KUMANO Keiki  The University of Tokyo, 医学部附属病院, 講師 (90396721)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsNotch / 白血病幹細胞 / ニッチ
Research Abstract

Murine bone marrow cells transformed by MLL-ENL induced AML in the culture for myeloid condition, and ALL in the culture for lymphoid condition. MLL-ENL induced AML cells were transduced with Notch1 active from and cultured on the OP-9 stromal cells. The one part of these cells expressed T cell specific surface marker. In the same way, AML cells trasduced with B cell gene (Pax5, E2A, EBF) expressed B cell marker.
AML cells were cultured on the Delta1 expressing OP-9 cells and activated by the Notch signaling. As a result, T cell differentiation was observed in the part of the AML cells. These results indicated that Multipotent cells existed in the MLL-ENL AML cells and the differentiation potential might be regulated by the niche signaling.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (27 results)

All 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 11 results) Presentation (2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] 造血細胞のリプログラミングの現状と血液疾患治療への応用2010

    • Author(s)
      熊野恵城
    • Journal Title

      血液・腫瘍科 60

      Pages: 460-464

    • NAID

      40019064565

    • Related Report
      2010 Final Research Report
  • [Journal Article] The role of Runx1/AML1 and Evi-1 in the regulation of hematopoietic stem cells.2010

    • Author(s)
      Kumano K, Kurokawa M.
    • Journal Title

      J Cell Physiol. 222

      Pages: 282-285

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hesl immortalizes committed progenitors and plays a role in blast crisis transition in chronic myelogenous leukemia.2010

    • Author(s)
      Nakahara F, Sakata-Yanagimoto M, Komeno Y, Kato N, Uchida T, Haraguchi K, Kumano K, Harada Y, Harada H, Kitaura J, Ogawa S, Kurokawa M, Kitamura T, Chiba S.
    • Journal Title

      Blood 115

      Pages: 2872-2881

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of Runx1/AML1 and Evi-1 in the regulation of he matopoietic stem cells.2010

    • Author(s)
      Kumano Keiki, Mineo Kurokawa
    • Journal Title

      J Cell Physiol.

      Volume: 222 Pages: 282-285

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 造血細胞のリプログラミングの現状と血液疾患治療への応用2010

    • Author(s)
      熊野恵城
    • Journal Title

      血液・腫瘍科

      Volume: 60 Pages: 460-464

    • NAID

      40019064565

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Dual antitumor mechanisms of Notch signaling inhibitor in a T-cell acute lymphoblastic leukemia xenograft model.2009

    • Author(s)
      Masuda S, Kumano K, Suzuki T, Tomita T, Iwatsubo T, Natsugari H, Tojo A, Shibutani M, Mitsumori K, Hanazono Y, Ogawa S, Kurokawa M, Chiba S.
    • Journal Title

      Cancer Sci. 100

      Pages: 2444-2450

    • NAID

      10027198807

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.2009

    • Author(s)
      Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S.
    • Journal Title

      Nature. 460

      Pages: 904-908

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma.2009

    • Author(s)
      Lee SY, Kumano K, Nakazaki K, Sanada M, Matsumoto A, Yamamoto G, Nannya Y, Suzuki R, Ota S, Ota Y, Izutsu K, Sakata-Yanagimoto M, Hangaishi A, Yagita H, Fukayama M, Seto M, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      Cancer Sci. 100

      Pages: 920-6

    • NAID

      10025145854

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Notch activation induces the generation of functional NK cells from human cord blood CD34-positive cells devoid of IL 15.2009

    • Author(s)
      Haraguchi K, Suzuki T, Koyama N, Kumano K, Nakahara F, Matsumoto A, Yokoyama Y, Sakata-Yanagimoto M, Masuda S, Takahashi T, Kamijo A, Takahashi K, Takanashi M, Okuyama Y, Yasutomo K, Sakano S, Yagita H, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      J Immunol. 182

      Pages: 6168-78

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Derivation of functional mature neutrophils from human embryonic stem cells.2009

    • Author(s)
      Yokoyama Y, Suzuki T, Sakata-Yanagimoto M, Kumano K, Higashi K, Takato T, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      Blood. 113

      Pages: 6584-92

    • NAID

      120007131544

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 白血病幹細胞を標的とした新規治療法2009

    • Author(s)
      熊野恵城,黒川峰夫
    • Journal Title

      Biotherapy 23

      Pages: 371-378

    • Related Report
      2010 Final Research Report
  • [Journal Article] 造血ニッチと幹細胞制御2009

    • Author(s)
      熊野恵城,黒川峰夫
    • Journal Title

      血液フロンティア 19

      Pages: 446-451

    • Related Report
      2010 Final Research Report
  • [Journal Article] 造血幹細胞2009

    • Author(s)
      熊野恵城,黒川峰夫
    • Journal Title

      医学のあゆみ 229

      Pages: 698-702

    • Related Report
      2010 Final Research Report
  • [Journal Article] 幹細胞の基礎研究:造血幹細胞2009

    • Author(s)
      熊野恵城,黒川峰夫
    • Journal Title

      医学のあゆみ 229

      Pages: 698-702

    • Related Report
      2010 Final Research Report
  • [Journal Article] The role of Runxl/AML1 and Evi-1 in the regulation of Hemato poietic Stem Cells2009

    • Author(s)
      Keiki Kumano, Mineo Kurokawa
    • Journal Title

      J.Cell.Physiol. 222

      Pages: 282-285

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 造血幹細胞2009

    • Author(s)
      熊野恵城、黒川峰夫
    • Journal Title

      医学のあゆみ 229

      Pages: 698-702

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 白血病幹細胞を標的とした新規治療法2009

    • Author(s)
      熊野恵城, 黒川峰夫
    • Journal Title

      Biotherapy 23

      Pages: 371-378

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Coordinated regulation of transcription factors through Notch2 is an important mediator of mast cell fate.2008

    • Author(s)
      Sakata-Yanagimoto M, Nakagami-Yamaguchi E, Saito T, Kumano K, Yasutomo K, Ogawa S, Kurokawa M, Chiba S.
    • Journal Title

      Proc Natl Acad Sci U S A. 105

      Pages: 7839-44

    • NAID

      120007138253

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Both Notchl and Notch2 contribute to the regulation of melanocyte homeostasis.2008

    • Author(s)
      Kumano K, Masuda S, Sata M, Saito To, Lee SY, Sakata-Yanagimoto M, Tomita T, Iwatsubo T, Natsugari H, Kurokawa M, Ogawa S, Chiba S.
    • Journal Title

      Pigment Cell Melanoma Res. 21

      Pages: 70-8

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] 造血器腫瘍におけるがん幹細胞研究の進展:AML幹細胞研究の進展2008

    • Author(s)
      熊野恵城、黒川峰夫
    • Journal Title

      血液・腫瘍科 56

      Pages: 694-700

    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Journal Article] 白血病幹細胞を標的とした新規治療法の開発2008

    • Author(s)
      熊野恵城、黒川峰夫
    • Journal Title

      医学のあゆみ 227

      Pages: 83-86

    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Journal Article] TEL-AML1関連小児白血病発症過程で、がん化過程を開始する細胞とがんを伝播する細胞2008

    • Author(s)
      熊野恵城、黒川峰夫
    • Journal Title

      分子細胞治療 7

      Pages: 470-471

    • Related Report
      2010 Final Research Report
  • [Presentation] Generation of Induced Pluripotent Stem Cells From Primary Chronic Myelogenous Leukemia Patient Sample.2010

    • Author(s)
      Keiki Kumano, Shunya Arai, Koki Ueda, et al.
    • Organizer
      52^<nd> ASH Annual Meeting
    • Place of Presentation
      Orland, Florida, USA.
    • Year and Date
      2010-12-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Generation of Induced Pluripotent Stem Cells From Primary Chronic Mvelogenous Leukemia Patient Sample.2010

    • Author(s)
      Keiki Kumano, Shunya Arai, Koki Ueda, et al.
    • Organizer
      52^<nd> ASH Annual Meeting.
    • Place of Presentation
      Orland, Florida, USA.
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Book] Annual Review血液2008

    • Author(s)
      熊野恵城、黒川峰夫
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Book] みんなに役立つ造血幹細胞移植の基礎と臨床2008

    • Author(s)
      熊野恵城、千葉滋
    • Publisher
      医薬ジャーナル社
    • Related Report
      2010 Final Research Report 2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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