Identification of therapeutic candidate targets specifically expressed in myeloma side population cells

• Project/Area Number: 25461406
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Akita University
• Principal Investigator: KAMEOKA YOSHIHIRO 秋田大学, 医学部, 准教授 (40422159)
• Co-Investigator(Kenkyū-buntansha): TAGAWA Hiroyuki 秋田大学, 医学系研究科, 講師 (30373492)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 多発性骨髄腫 / SP細胞 / 遺伝子発現 / 骨髄腫 / miRNA / miR-181 / microRNA / side population

Outline of Final Research Achievements

We conducted comparison of miRNA/gene expression between SP and non-SP cells in multiple myeloma. We found that SP showed stem cell like phenotypes. We purified SP cells from myeloma cell lines and detected that miR-181 family’s downregulation in SP cells. Moreover we found that Bmi-1 is a possible target of miR-181, and finally revealed following mechanism: EZH2 activation->miR-181 downregulation->downregulation of Bim or Pten->Bcle downregulation MM cells.

Research Products

• [Journal Article] Lymphoma-Associated hemophagocytic syndrome. (2015)
  • Author(s): 亀岡吉弘, 髙橋直人
  • Journal Title: 日本臨牀 Volume: 73 Pages: 455-460
• [Journal Article] 骨髄腫幹細胞研究の進展 (2015)
  • Author(s): 池田 翔, 田川博之
  • Journal Title: 血液内科 Volume: 70 Pages: 661-667
• [Journal Article] Analysis of clinical characteristics and prognostic factors for angioimmunoblastic T-cell lymphoma. (2015)
  • Author(s): Kameoka Y, Takahashi N, Itou S, Kume M, Noji H, Kato Y, Ichikawa Y, Sasaki O, Motegi M, Ishiguro A, Tagawa H, Ishizawa K, Ishida Y, Ichinohasama R, Harigae H, Sawada K.
  • Journal Title: Int J Hematol Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] R-GDP therapy as salvage treatment of patients with refractory or relapsed DLBCL (2015)
  • Author(s): Kameoka,Y., Ubukawa,K., Nara,M., Yokoyama, H., Ito,S., Ishizawa,K., Ishida,Y., Harigae,H., TakahashiN
  • Organizer: 日本血液学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Presentation] Chemokine CCL20 and its receptor CCR6 are new therapeutic targets in cutaneous T-cell lymphoma (2015)
  • Author(s): Ikeda,S., Kitadate,A., Ito,M., Teshima,K., Nara,M., Watanabe,A., Ubukawa,K., Fujishima,M., Fujishima,N., Yoshioka,T., Kameoka,Y., Takahashi,N., Tagawa,H
  • Organizer: 日本血液学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Presentation] Tumor-suppressor miR-16 induces senescence and apoptosis in aggressive T-cell lymphomas. (2015)
  • Author(s): 北舘明宏, 池田 翔, 手島和暁, 伊藤 貢, 奈良美保, 鵜生川久美, 渡部 敦, 藤島眞澄, 藤島直仁, 吉岡智子, 亀岡吉弘, 髙橋直人, 宮垣朝光, 菅谷 誠, 田川博之
  • Organizer: 日本血液学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Presentation] Analysis of the MCNU-based high dose chemotherapy followed by ASCT for relapsed or refractory DLBCL (2014)
  • Author(s): 亀岡 吉弘、高橋 直人、赤木 智昭、奈良 美保、井根 省二、加藤 裕一、横山 寿行、野地 秀義、伊藤 薫樹、石田 陽治、張替 秀郎、澤田 賢一(2014)
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-10 – 2014-10-13