The effect of exosomal miRNA on AML/MDS stromal cells

• Project/Area Number: 15K09482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Sapporo Medical University
• Principal Investigator: Kobune Masayoshi 札幌医科大学, 医学部, 准教授 (90336389)
• Co-Investigator(Kenkyū-buntansha): 佐藤 勉 札幌医科大学, 医学部, 講師 (40404602) ; 堀口 拓人 札幌医科大学, 医学部, 研究員 (70634674) ; 高田 弘一 札幌医科大学, 医学部, 講師 (90398321) ; 村瀬 和幸 札幌医科大学, 医学部, 講師 (90444918)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: エクソソーム / マイクロRNA / 白血病 / 骨髄異形成症候群 / 骨髄間質細胞 / PCBP1 / エキソソーム / 間葉系幹細胞 / 骨髄間質 / 白血病幹細胞 / 細胞外小胞

Outline of Final Research Achievements

The failure of normal hematopoiesis is observed in myeloid neoplasms. However, the precise mechanisms governing replacement of normal hematopoietic stem cells in their niche by myeloid neoplasm stem cells have not been clarified yet. Primary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells induced aberrant expression of multiple hematopoietic factors including JAG1, SCF and ANGPT1 in mesenchymal stem cells. Importantly, transfer of myeloid neoplasm-derived extracellular vesicles reduced the hematopoietic-supportive capacity of mesenchymal stem cells. Analysis of exosomal microRNA indicated that several species including miR-7977 from acute myeloid leukemia cells were higher than those from normal CD34+ cells. Remarkably, the copy number of miR-7977 in BM interstitial fluid was elevated in not only AML, but also MDS, as compared with control bone marrow. Thus, miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis.

Research Products

• [Journal Article] Small molecule CP-31398 induces reactive oxygen species-dependent apoptosis in human multiple myeloma (2017)
  • Author(s): Arihara Yohei、Takada Kohichi、Kamihara Yusuke、Hayasaka Naotaka、Nakamura Hajime、Murase Kazuyuki、Ikeda Hiroshi、Iyama Satoshi、Sato Tsutomu、Miyanishi Koji、Kobune Masayoshi、Kato Junji
  • Journal Title: Oncotarget Volume: 8 Issue: 39 Pages: 65889-65899
  • DOI: 10.18632/oncotarget.19508
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial. (2015)
  • Author(s): Hirayama Y, Ishitani K, Sato Y, Iyama S, Takada K, Murase K, Kuroda H, Nagamachi Y, Konuma Y, Fujimi A, Sagawa T, Ono K, Horiguchi H, Terui T, Koike K, Kusakabe T, Sato T, Takimoto R, Kobune M, Kato J
  • Journal Title: Int J Clin Oncol Volume: 20 Issue: 5 Pages: 866-871
  • DOI: 10.1007/s10147-015-0810-y
  • Peer Reviewed
• [Journal Article] Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer. (2015)
  • Author(s): Ishiwatari H, Hayashi T, Kato J, et al.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 75 Issue: 4 Pages: 805-812
  • DOI: 10.1007/s00280-015-2704-0
  • Peer Reviewed / Open Access
• [Journal Article] Increased duodenal iron absorption through upregulation of DMT1 due to enhancement of IRP1 activity in patients with NASH. (2015)
  • Author(s): Hoki T, Miyanishi K, Kato J, et al.
  • Journal Title: Hepatology Volume: 印刷中 Issue: 3 Pages: 751-761
  • DOI: 10.1002/hep.27774
  • Peer Reviewed / Open Access
• [Presentation] PCBP1発現低下による骨髄間質細胞の機能不全発症機序の解析 (2017)
  • Author(s): 小船雅義、堀口拓人、宮西浩嗣、加藤淳二
  • Organizer: 日本鉄バイオサイエンス学会
  • Invited
• [Presentation] Extracellular vesicle microRNAs from acute myeloid leukemia are involved in the regulation of adherence junction in bone marrow microenvironment. (2016)
  • Author(s): Masahiro Yoshida, Masayoshi Kobune, et al.
  • Organizer: American Society of Hematology
  • Place of Presentation: サンディエゴ
  • Year and Date: 2016-12-01
  • Int'l Joint Research
• [Presentation] Exosomal microRNAs in bone marrow cavity induce stromal dysfunction in AML/MDS (2015)
  • Author(s): Hiroto Horiguchi, Masayoshi Kobune, Shohei Kikuchi, Kazuyuki Murase, Satoshi Iyama, Kohichi Takada, Tsutomu Sato, Yasushi Sato1), Koji Miyanishi1), Rishu Takimoto, Hiroyuki Kuroda, Masahiro Maeda, Junji Kato
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県金沢市 ホテル日航金沢
  • Year and Date: 2015-10-16
• [Book] 今日の治療指針2015：鉄欠乏性貧血 (2015)
  • Author(s): 小船雅義
  • Total Pages: 4
  • Publisher: 医学書院
• [Book] 今日の診断指針2015：鉄欠乏性貧血 (2015)
  • Author(s): 小船雅義
  • Total Pages: 2
  • Publisher: 医学書院