Analysis of Multiple myeloma pahtophysiology using xenograft model having humanized BM microenvironment

• Project/Area Number: 23500501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Tokai University
• Principal Investigator: MUGURUMA Yukari 東海大学, 医学部, 助教 (80398750)
• Co-Investigator(Kenkyū-buntansha): ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014) ; YAHATA Takashi 東海大学, 医学部, 准教授 (10398753)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: multiple myeloma / humanized mice / xenograft / microenvironment / 多発性骨髄腫 / Notch / 骨髄微小環境

Research Abstract

Multiple myeloma is a hematopoietic malignancy characterized by proliferation of malignant plasma cells and concomitant hematopoietic suppression as well as bone disease. Although Notch signal has been implicated in pathogenesis of multiple myeloma, its precise role is unknown. We created a myeloma mouse model by transplanting human myeloma cells into previously established immunodeficient mice that express human Jagged1 in osteoblastic manner. We demonstrated that Jagged1-Notch signal supported survival and proliferation of myeloma cells in bone marrow. Furthermore, Jagged1-Nocth signal directly promoted drug resistance in vivo and in vitro.

Research Products

• [Journal Article] Establishment of a xenograft model of human myelodysplastic syndromes (2011)
  • Author(s): Muguruma Y, Matsushita H, Yahata T, Yumino S, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, Ando K
  • Journal Title: Haematologica Volume: 96(4) Pages: 543-51
  • Peer Reviewed
• [Journal Article] Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells (2011)
  • Author(s): Yahata T, Takanashi T, Muguruma Y, Ibrahim AA, Matsuzawa H, Uno T, Sheng Y, Onizuka M, Ito M, Kato S, Ando K
  • Journal Title: Blood Volume: 118(11) Pages: 2941-50
  • NAID: 40019489714
  • Peer Reviewed
• [Journal Article] Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells (2011)
  • Author(s): Yahata, T.
  • Journal Title: Blood Volume: 118 Issue: 11 Pages: 2941-2950
  • DOI: 10.1182/blood-2011-01-330050
  • NAID: 40019489714
  • Peer Reviewed
• [Journal Article] Establishment of xenograft model of human myelodysplastic syndromes (2011)
  • Author(s): Muguruma Y, Matsushita H, Yahata H, Yumino S, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, Ando K
  • Journal Title: Haematologica Volume: 96 Issue: 4 Pages: 543-551
  • DOI: 10.3324/haematol.2010.027557
  • Peer Reviewed
• [Presentation] CD34+/CD38+ cells from human cord blood initiate APL by induction of PML-RARA (2012)
  • Author(s): Matsushita H, Yahata T, Nakamura Y, Sheng Y, Muguruma Y, Matsuzawa H, Uno T, Takanashi T, Ando K
  • Organizer: JSH International Symposium
  • Place of Presentation: 川越プリンスホテル
• [Presentation] Non-telomeric stem cell aging in hematopoietic regeneration (2012)
  • Author(s): Yahata T, Takanashi T, Muguruma Y, Ibrahim AA, Matsuzawa H, Uno T, Sheng Y, Onizuka M, Ito M, Kato S, Ando K
  • Organizer: 第74回日本血液学会
  • Place of Presentation: 京都国際会議場
• [Presentation] CD34+/CD38+ cells from human cord blood onotoate APL by induction of PML-RARA (2012)
  • Author(s): Hiromichi Matsushita, Takashi Yahata, Yoshihiko Nakamura, Yin Sheng, Yukari Muguruma, et al.
  • Organizer: JSH International Symposium
  • Place of Presentation: Kawagoe Prince Hotel
• [Presentation] Non-telomeric stem cell aging in hematopoietic regeneration (2012)
  • Author(s): Takashi Yahata, Tomoni Takanashi, Yukari Muguruma, Abd Aziz Ibrahim, Hiedyuki Matsuzawa, Tomoko Uno, Yin Sheng, Makoto Onizuka, Mamoru Ito, Shyunichi Kato, Kiyoshi Ando
  • Organizer: 日本血液学会
  • Place of Presentation: 京都国際会議場
• [Presentation] CD34+/CD38+ cells from human cord blood initiate APL by induction of PML-RARA (2011)
  • Author(s): Matsushita H, Yahata T, Nakamura Y, Sheng Y, Muguruma Y, Matsuzawa H, Uno T, Takanashi T, Ando K
  • Organizer: 第73回日本血液学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-15
• [Presentation] CD34+/CD38+cells from human cord blood initiate APL by induction of PML-RARA
  • Author(s): Hiromichi Matsushita, Takashi Yahata, Yoshihiko Nakamura, Yin Sheng, Yukari Muguruma, Hideyuki MAtsuzawa, Tomoko Uno, Tomomi Takanashi, Kiyoshi Ando
  • Organizer: 日本血液学会
  • Place of Presentation: 名古屋国際会議場
• [Remarks]
  • URL: http://www.med.u-tokai.ac.jp/daigakuin/web/saisei.html