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

2013 Fiscal Year Final Research Report

• 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: 中山 ゆかり (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
• Keywords: multiple myeloma / humanized mice / xenograft / microenvironment

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
  • Peer Reviewed
• [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
  • Year and Date: 20121019-21
• [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
  • Year and Date: 20120526-27
• [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
• [Remarks]
  • URL: http://www.med.u-tokai.ac.jp/daigakuin/web/saisei.html