The role of Notch signaling in the leukemia stem cells.

• Project/Area Number: 20591111
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: The 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: ¥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)
• Keywords: Notch / 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.

Research Products

• [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
• [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
  • 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
  • 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
  • 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
• [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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [Journal Article] The role of Runxl/AML1 and Evi-1 in the regulation of Hemato poietic Stem Cells (2009)
  • Author(s): Keiki Kumano, Mineo Kurokawa
  • Journal Title: J.Cell.Physiol. 222 Pages: 282-285
  • 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
• [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
• [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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [Book] Annual Review血液 (2008)
  • Author(s): 熊野恵城、黒川峰夫
  • Publisher: 中外医学社
• [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
• [Remarks] ホームページ等