Altered Exosomal miRNA expression of late onset acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.

• Project/Area Number: 26860373
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Tokyo Medical University
• Principal Investigator: Yoshizawa Seiichiro 東京医科大学, 医学部, 助教 (70421063)
• Research Collaborator: UMEZU Tomohiro 東京医科大学, 医学部, 講師 (40385547)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); 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)
• Keywords: 移植片対宿主病 / 造血幹細胞移植 / エクソソーム / miRNA / リキッドバイオプシー

Outline of Final Research Achievements

Exosomes, small endosome-derived extracellular vesicles, are present in various biological fluids, such as plasma, thus have potential in facilitating molecular diagnosis. The aim of this study is to determine clinically relevant exosomal miRNAs in patients developing LA GVHD after HSCT.
We evaluated blood samples obtained from 10 patients who underwent HSCT for treatment of hematologic diseases. Exosomal miRNA profiling was done using a TaqMan low-density array.
We found that a subset of miRNAs was significantly up-regulated in the exosomes of LA GVHD groups compared to non-GVHD controls. Accordingly, the predicted target genes of altered miRNAs were extracted by MirTarBase. To estimate the biological implication of LA GVHD related miRNAs, we then investigated comprehensively possible related pathway using DAVID bioinformatics tools. Our study indicates that altered expression of certain exosomal miRNAs may play an important role in the immunoregulation of LA GVHD.

Research Products

• [Journal Article] <i>BCR-ABL1</i>-positive chronic myeloid leukemia emerging in a patient with secondary myelofibrosis harboring the <i>JAK2</i>-V617F mutation (2017)
  • Author(s): Amemiya A, Ito Y, Ishibashi Y, Saito Y, Katagiri S, Suguro T, Asano M, Yoshizawa S, Akahane D, Tanaka Y, Fujimoto H, Okabe S, Gotoh M, Tauchi T, Ohyashiki K.
  • Journal Title: Rinsho Ketsueki Volume: 58 Issue: 4 Pages: 298-302
  • DOI: 10.11406/rinketsu.58.298
  • NAID: 130006882220
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] Musculoskeletal pain after stopping tyrosine kinase inhibitor in patients with chronic myeloid leukemia: a questionnaire survey (2016)
  • Author(s): Katagiri S, Tauchi T, Saito Y, Suguro T, Asano M, Yoshizawa S, Sakuta J, Akahane D, Tanaka Y, Furuya N, Ando K, Fujimoto H, Okabe S, Gotoh M, Ito Y, Ohyashiki K.
  • Journal Title: Rinsho Ketsueki Volume: 57 Issue: 7 Pages: 873-876
  • DOI: 10.11406/rinketsu.57.873
  • NAID: 130005254872
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] Treatment-free molecular remission achieved by combination therapy with imatinib and IFNα in CML with <i>BIM</i> deletion polymorphism relapsed after stop imatinib (2015)
  • Author(s): Katagiri S, Tauchi T, Umezu T, Saito Y, Suguro T, Asano M, Yoshizawa S, Kitahara T, Akahane D, Tanaka Y, Fujimoto H, Okabe S, Gotoh M, Ito Y, Ohyashiki JH, Ohyashiki K
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 2 Pages: 216-219
  • DOI: 10.11406/rinketsu.56.216
  • NAID: 130004920704
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] Human herpesvirus 6 reactivation on the 30th day after allogeneic hematopoietic stem cell transplantation can predict grade 2-4 acute graft-versus-host disease. (2014)
  • Author(s): Gotoh M, Yoshizawa S, Katagiri S, Suguro T, Asano M, Kitahara T, Akahane D, Okabe S, Gotoh A, Tauchi T, Ito Y, Ohyashiki K
  • Journal Title: Transplant Infectious Disease Volume: 16(3) Issue: 3 Pages: 440-449
  • DOI: 10.1111/tid.12229
  • Peer Reviewed
• [Journal Article] A novel reduced-intensity umbilical cord blood transplantation using a recombinant G-CSF combined with high-dose Ara-C for active myeloid malignancies (2014)
  • Author(s): Gotoh M, Yoshizawa S, Katagiri S, Suguro T, Asano M, Kitahara T, Akahane D, Okabe S, Gotoh A, Tauchi T, Ito Y, Ohyashiki K
  • Journal Title: Bone Marrow Transplantation Volume: 49(7) Issue: 7 Pages: 955-960
  • DOI: 10.1038/bmt.2014.66
  • Peer Reviewed
• [Presentation] 骨髄間質細胞が放出するエクソソーム内加齢関連miRNAの同定と機能解析 (2016)
  • Author(s): 関野知聖、梅津知宏、吉澤成一郎、大屋敷一馬、大屋敷純子
  • Organizer: 第178回東京医科大学医学会総会
  • Place of Presentation: 東京
  • Year and Date: 2016-11-05
• [Presentation] Anti-angiogenic effect of normal bone marrow stromal cell-derived exosomes rejuvenated by miR-340. (2016)
  • Author(s): Umezu T, Imanishi S, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki J
  • Organizer: The 78th Annual Meeting of Japanese Society of Hematology
  • Place of Presentation: Yokohama
  • Year and Date: 2016-10-13
• [Presentation] Mutation analysis of bone marrow stromal cells derived from AML and MDS. (2016)
  • Author(s): Azuma K, Umezu T, Imanishi S, Asano M, Yoshizawa S, Katagiri S, Ohyashiki K, Ohyashiki JH
  • Organizer: The 78th Annual Meeting of Japanese Society of Hematology
  • Place of Presentation: Yokohama
  • Year and Date: 2016-10-13
• [Presentation] Exosomal miRNA signature of late onset acute graft-versus-host disease in allogenic hematopoietic stem cell transplantation. (2015)
  • Author(s): Yoshizawa S, Umezu T, Saitoh Y, Gotoh M, Akahane D, Kobayashi C, Ohyashiki JH, Ohyashiki K
  • Organizer: 第77回日本血液学会学術集会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Presentation] Exosomal miRNA signature of bone marrow mesenchymal stromal cells derived from MDS patients. (2015)
  • Author(s): Saitoh Y, Imanishi S, Umezu T, Yoshizawa S, Asano M, Fujimoto H, Akahane D, Yamamoto Y, Kobayashi C, Ohyashiki JH, Ohyashiki K
  • Organizer: 第77回日本血液学会学術集会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Presentation] Exosome-based therapeutic approach using exosomal miRNAs derived from bone marrow mesenchymal stromal cells. (2015)
  • Author(s): Umezu T, Imanishi S, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki JH
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Bone marrow mesenchymal stromal cells from healthy donors secrete exosomes that inhibit in vivo tumor growth and angiogenesis in multiple myeloma. (2015)
  • Author(s): Umezu T, Imanishi S, Azuma K, Yoshizawa S, Ohyashiki K, Ohyashiki JH
  • Organizer: 20th Congress of European Hematology Association (EHA)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Distinct exosomal miRNA expression of late onset graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. (2015)
  • Author(s): Yoshizawa S, Umezu T, Saitoh Y, Gotoh M, Akahane D, Kobayashi C, Ohyashiki JH, Ohyashiki K
  • Organizer: 20th Congress of European Hematology Association (EHA)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11
  • Int'l Joint Research
• [Presentation] Age-related alterations in exosomal miRNAs derived from bone marrow mesenchymal stromal cells. (2015)
  • Author(s): Umezu T, Imanishi S, Yoshizawa S, Saitoh Y, Yamamoto Y, Ohyashiki K, Ohyashiki JH
  • Organizer: 6th JSH International Symposium 2015
  • Place of Presentation: 軽井沢
  • Year and Date: 2015-05-22
• [Presentation] 同種造血幹細胞移植のGVHDに特異的なexosomal miRNAの解析 (2014)
  • Author(s): 吉澤成一郎
  • Organizer: 第174回東京医科大学医学会総会
  • Place of Presentation: 東京（新宿）
  • Year and Date: 2014-11-01