Leukemic stem cell in humanized mouse bone marrow niche

• Project/Area Number: 21791008
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Keio University
• Principal Investigator: SHIMA Haruko Keio University, 医学部, 助教 (80424167)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 造血幹細胞 / ニッチ / 白血病 / 急性骨髄性白血病 / 白血病幹細胞 / M-CSFR / NOGマウス / 細胞周期 / 低酸素

Research Abstract

Using humanized mouse model, we showed that human hematopoietic stem cells acquired hypoxic state between 4 and 8 weeks after transplantation, followed by acquisition of quiescent state between 8 and 12 weeks after transplantation, and localized in endosteal lesion of engrafted bone marrow. We also developed MOZ-TIF2 induced AML mouse model and demonstrated that AML stem cells expressed high levels of M-CSFR. Further study is expected to analyze AML stem cells using humanized mouse model.

Research Products

• [Journal Article] 幹細胞生物学からみたAML治療の新たな方向性 (2011)
  • Author(s): 嶋晴子、北林一生
  • Journal Title: 血液内科 62巻、4号 Pages: 98-105
• [Journal Article] MOZ-TIF2白血病における白血病幹細胞の生成機構 (2011)
  • Author(s): 嶋晴子、北林一生
  • Journal Title: 血液内科 62巻、1号 Pages: 409-414
  • NAID: 40019064537
• [Journal Article] MOZ-TIF2白血病における白血病幹細胞の生成機構 (2011)
  • Author(s): 嶋晴子, 北林一生
  • Journal Title: 血液内科 Volume: 62 Pages: 98-105
  • NAID: 40019064537
• [Journal Article] Acquisition of G(0) state by CD34-positive cord blood cells after bone marrow transplantation. (2010)
  • Author(s): Shima H, Takubo K, Tago N, Iwasaki H, Arai F, Takahashi T, Suda T.
  • Journal Title: Experimental Hematology. Vol.38、No.12 Pages: 1231-1240
  • Peer Reviewed
• [Journal Article] PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. (2010)
  • Author(s): Aikawa Y, Katsumoto T, Zhang P, Shima H, Shino M, Terui K, Ito E, Ohno H, Stanley ER, Singh H, Tenen DG, Kitabayashi I.
  • Journal Title: Nature Medicine. Vol.16、No.5 Pages: 580-585
  • Peer Reviewed
• [Journal Article] Acquisition of G_0 state by CD34-positive cord blood cells after bonemarrow transplantation. (2010)
  • Author(s): Shima H, Takubo K, Tago N, Iwasaki H, Arai F, Takahashi T,Suda T.
  • Journal Title: Experimental Hematology Volume: 38 Pages: 1231-1240
  • Peer Reviewed
• [Presentation] Regulation of stem cells in MOZ and other leukemias (2010)
  • Author(s): Haruko Shima, Yukiko Aikawa, Kumiko Yamanaka, Takuo Katsumoto, Mika Shino, Akihiko Koseki, Issay Kitabayashi
  • Organizer: 第8回幹細胞シンポジウム
  • Place of Presentation: 淡路
  • Year and Date: 2010-05-14
• [Presentation] Regulation of stem cells in MOZ and other leukemias (2010)
  • Author(s): Haruko Shima
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 淡路(兵庫県)
  • Year and Date: 2010-05-14
• [Presentation] Acquisition of G0 state in CD34-positive cord blood cells after bone marrow transplantation. (2009)
  • Author(s): Haruko Shima, Keiyo Takubo, Naoko Tago, Hiroko Iwasaki, Kentaro Hosokawa, Hiroki Yoshihara, Fumio Arai, Takao Takahashi, Issay Kitabayashi, Toshio Suda.
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] Acquisition of GO state in CD34-positive cord blood cells after bone marrow transplantation (2009)
  • Author(s): 嶋晴子
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23