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Development of novel diagnostics for hematological malignancy on basis of the exosome analysis

Research Project

Project/Area Number 15H04303
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor diagnostics
Research InstitutionTokyo Medical University

Principal Investigator

Ohyashiki Kazuma  東京医科大学, 医学部, 主任教授 (20201387)

Co-Investigator(Kenkyū-buntansha) 大屋敷 純子  東京医科大学, 医学部, 教授 (20191950)
梅津 知宏  東京医科大学, 医学部, 講師 (40385547)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
KeywordsmiRNA / 細胞外小胞 / 骨髄異形成症候群 / 骨髄間質細胞 / エクソソーム / 造血器腫瘍
Outline of Final Research Achievements

Bone marrow stromal cells (BMSCs) play an important role in bone marrow environment. Recent evidences suggest that extracellular vesicles (EVs) act as a mediator of cell-cell interaction in hematologic neoplasms. To clarify the possible association between the cargo of BMSC-EVs and disease severity, we performed miRNA profiling in BMSC-EVs derived from MDS patients.
BMSCs from 29 MDS patients were obtained by classical adhesion methods. We tentatively separated MDS patients into two groups according to the IPSS-R: low-risk and high-risk group. We found that a subset of EV-miRNA was differentially expressed between the two groups. Among them, we in particular focus on EV-miR-101: the expression level was significantly lower in high-risk MDS. Cell-cell communication via EV-miR-101 may play in part some role between BMSC and MDS cells. Our study shed light on the biological relevance of BMSC-EV and EV-miRNA in MDS bone marrow microenvironment.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (43 results)

All 2018 2017 2016 2015

All Journal Article (13 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (26 results) (of which Int'l Joint Research: 16 results) Book (4 results)

  • [Journal Article] Extracellular vesicle (EV)- mediated cell-cell communication in hematologic neoplasms2018

    • Author(s)
      Ohyashiki JH, Umezu T, Ohyashiki K
    • Journal Title

      Philosophical Transactions of the Royal Society B: Biological Sciences

      Volume: 373 Issue: 1737 Pages: 1737-1737

    • DOI

      10.1098/rstb.2016.0484

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia2017

    • Author(s)
      Katagiri S, Umezu T, Asano M, Akahane D, Azuma K, Makishima H, Yoshida K, Watatani Y, Chiba K, Miyano S, Ogawa S, Ohyashiki JH, Ohyashiki K
    • Journal Title

      Leukemia and Lymphoma

      Volume: 3 Issue: 6 Pages: 1-4

    • DOI

      10.1080/10428194.2017.1382696

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Upregulated exosomal miRNA-140-3p in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors2017

    • Author(s)
      Asano M, Umezu T, Katagiri S, Kobayashi C, Tauchi T, Gotoh M, Ando K, Okabe S, Ohyashiki JH, Ohyashiki K
    • Journal Title

      Int J Hematol

      Volume: 105(4) Issue: 4 Pages: 419-422

    • DOI

      10.1007/s12185-017-2199-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phase 1/2 study of the WT1 peptide cancer vaccine WT4869 in patients with myelodysplastic syndrome2017

    • Author(s)
      Ueda Yasunori、Ogura Michinori、Miyakoshi Shigesaburo、Suzuki Takahiro、Heike Yuji、Tagashira Shuzo、Tsuchiya Satoru、Ohyashiki Kazuma、Miyazaki Yasushi
    • Journal Title

      Cancer Science

      Volume: 108 Issue: 12 Pages: 2445-2453

    • DOI

      10.1111/cas.13409

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis.2017

    • Author(s)
      Umezu T, Imanishi S, Azuma K, Kobayashi C, Yoshizawa S, Ohyashiki K, Ohyashiki JH.
    • Journal Title

      Blood Adv

      Volume: 1(13) Issue: 13 Pages: 812-823

    • DOI

      10.1182/bloodadvances.2016003251

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Teriflunomide restores 5-azacytidine sensitivity via activation of pyrimidine salvage in 5-azacytidine-resistant leukemia cells.2017

    • Author(s)
      Imanishi S, Takahashi R, Katagiri S, Kobayashi C, Umezu T, Ohyashiki K, Ohyashiki JH.
    • Journal Title

      Oncotarget

      Volume: 8(41) Issue: 41 Pages: 69906-69915

    • DOI

      10.18632/oncotarget.19436

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic variations of bone marrow mesenchymal stromal cells derived from acute leukemia and myelodysplastic syndrome by targeted deep sequencing.2017

    • Author(s)
      Azuma K, Umezu T, Imanishi S, Asano M, Yoshizawa S, Katagiri S, Ohyashiki K, Ohyashiki JH.
    • Journal Title

      Leuk Res

      Volume: 62 Pages: 23-28

    • DOI

      10.1016/j.leukres.2017.09.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exosomes promote bone marrow angiogenesis in hematologic neoplasia: the role of hypoxia.2016

    • Author(s)
      Ohyashiki JH, Umezu T, Ohyashiki K
    • Journal Title

      Curr Opin Hematol

      Volume: 23(3) Issue: 3 Pages: 268-273

    • DOI

      10.1097/moh.0000000000000235

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Down-regulation of plasma miR-215 in chronic myeloid leukemia patients with successful imatinib discontinuation.2016

    • Author(s)
      Ohyashiki K, Umezu T, Katagiri S, Kobayashi C, Azuma K, Tauchi T, Okabe S, Fukuoka Y, Ohyashiki JH
    • Journal Title

      The International Journal of Molecular Sciences

      Volume: 17(4) Issue: 4 Pages: 570-570

    • DOI

      10.3390/ijms17040570

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Validation of cytogenetic risk groups according to International Prognostic Scoring Systems by peripheral blood CD34+ FISH: Results from a German diagnostic study in comparison with an international control group.2015

    • Author(s)
      Braulke F, Ohyashiki K, et al
    • Journal Title

      Haematologica

      Volume: 100(2) Issue: 2 Pages: 205-213

    • DOI

      10.3324/haematol.2014.110452

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Frequency of del(12p) is commonly undetermined in myelodysplastic syndromes: Results from a German diagnostic study in comparison with an international control group.2015

    • Author(s)
      Braulke F, Ohyashiki K, et al
    • Journal Title

      Genes Chromosomes and Cancer

      Volume: 54(12) Issue: 12 Pages: 809-817

    • DOI

      10.1002/gcc.22292

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] effect of deferasirox with 5-azacytidine in human leukemia cells in vitro.2015

    • Author(s)
      Imanishi S, Takahashi R, Ohsuga M, Ohyashiki K, Ohyashiki JH
    • Journal Title

      Annals of Hematology

      Volume: 94(9) Issue: 9 Pages: 1601-1602

    • DOI

      10.1007/s00277-015-2417-9

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 造血器腫瘍におけるエクソソームを介した細胞間相互作用機構:多発性骨髄腫を中心に2015

    • Author(s)
      梅津知宏、大屋敷純子、大屋敷一馬
    • Journal Title

      血液内科

      Volume: 71(3) Pages: 396-400

    • Related Report
      2015 Annual Research Report
  • [Presentation] Combining effects of the SMO inhibitor and JAK1 inhibitor in MDS-derived induced potent stem cells (iPS)2017

    • Author(s)
      Tauchi T, Okabe S, Katagiri S, Tanaka Y, Ohyashiki K
    • Organizer
      22th European Hematology Association
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] miRMA profiling of circulating extracellular vesicles in CML patients with musculoskeletal pain associated with discontinuation of tyrosine kinase inhibitors2017

    • Author(s)
      Ohyashiki K, Asano M, Umezu T, Katagiri S, Kobayashi C, Tauchi T, Gotoh M, Ando K, Okabe S, Ohyashiki K
    • Organizer
      22th European Hematology Association
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of extracellular vesicle secretion induces apoptosis of bone marrow stromal cells: Towards soil-targeted therapy in multiple myeloma2017

    • Author(s)
      Umezu T, Imanishi S, Yoshizawa S, Ohyashiki K, Ohyashiki JH
    • Organizer
      22th European Hematology Association
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Extracellular vesicles (EVs) released by bone marrow stromal cells show a distinct miRNA profiling in high-risk MDS patients2017

    • Author(s)
      Ohyashiki K, Saitoh Y, Imanishi S, Umezu T, Yoshizawa S, Asano M, Fujimoto H, Akahane D, Kobayashi C, Ohyashiki JH
    • Organizer
      The 14th International Symposium on Myelodysplastic Syndromes
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Teriflunomide restores 5-azacytidine sensitivity via activation of pyrimidine salvage in 5-azacytidine-resistant leukemia cells2017

    • Author(s)
      Imanishi S, Takahashi R, Katagiri S, Umezu T, Kobayashi C, Ohyashiki K, Ohyashiki JH
    • Organizer
      The 14th International Symposium on Myelodysplastic Syndromes
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Molecular signatures that predict response to azacitidine treatment for myelodysplastic syndromes2017

    • Author(s)
      Nannya Y, Takeda J, Sato S, Shiozawa Y, Shiraishi Y, Kataoka K, Chiba K, Tanaka H, Chiba S, Asou N, Kiyoi H, Imai K, Hirase C, Dobashi N, Kiguchi T, Nakao S, Ohyashiki K, Miyazaki Y, Naoe T, Makishima H, Miyano S, Kenichi Yoshida K, Ogawa S*
    • Organizer
      59th ASH annual meeting and exposition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Combining effects of the SMO inhibitor and BCL-2 inhibitor in MDS-derived induced potent stem cells (iPS)2017

    • Author(s)
      Tauchi T, Okabe S, Katagiri S, Tanaka Y, Ohyashiki K
    • Organizer
      59th ASH annual meeting and exposition
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RUNX2 super enhancer promotes the development of blastic plasmacytoid dendritic cell neoplasm. 21th RUNX meeting2017

    • Author(s)
      Sashida G, Kubota S, Tokunaga K, Oshima M, Umezu T, Kanai A, Tan KT, Yang H, Iwanaga E, Asou N, Maeda T, Iwama A, Ohyashiki K, Osato M
    • Organizer
      21th RUNX meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of extracellular vesicle secretion induces apoptosis of bone marrow stroma cells2017

    • Author(s)
      Umezu T, Imanishi S, Yoshizawa Sm Ohyashiki K, Ohyashiki JH
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 慢性骨髄性白血病におけるチロシンキナーゼ阻害薬中止後の筋骨格痛ではエクソソームmiR-140-3pの上昇がみられる2016

    • Author(s)
      浅野倫代、梅津知宏、片桐誠一朗、小林千晶、田内哲三、岡部聖一、大屋敷純子、大屋敷一馬
    • 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
    • Related Report
      2016 Annual Research Report
  • [Presentation] アザシチジン耐性白血病細胞におけるヒストン化学修飾の役割の解明2016

    • Author(s)
      髙橋諒子、今西 哲、梅津知宏、小林千晶、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
    • Related Report
      2016 Annual Research Report
  • [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
    • Related Report
      2016 Annual Research Report
  • [Presentation] Mutation analysis of bone marrow stromal cells derived from AML and MDS2016

    • Author(s)
      Azuma K, Umezu T, Imanishi S, Asano M, Yoshizawa S, Katagiri S, Ohyashiki K, Ohyashiki JH
    • Organizer
      第78回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clonal evolution in AML which relapsed 15 years after BMT2016

    • Author(s)
      Katagiri S, Azuma K, Umezu T, Akahane D, Wataya Y, Yoshida K, Makishima H, Ogawa S, Ohyashiki JH, Ohyashiki K
    • Organizer
      第78回日本血液学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Clinical relevance of plasma miR-215 level in CML patients treated with imatinib2016

    • Author(s)
      Katagiri S, Umezu T, Kobayashi C, Azuma K, Tauchi T, Okabe S, Ohyashiki JH, Ohyashiki K
    • Organizer
      7th JSH International Symposium
    • Place of Presentation
      Awajishima
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Toward exosome-based cancer therapy: rejuvenation of exosomes derived from normal bone stroma cells2016

    • Author(s)
      Umezu T, Imanishi S, Azuma K, Kobayashi C, Ohyashiki K, Ohyashiki JH
    • Organizer
      ISEV 2016
    • Place of Presentation
      Rotterdam
    • Year and Date
      2016-05-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone marrow stromal cells from young healthy donors secrete exosomes that inhibit in vivo angiogenesis in multiple myeloma.2016

    • Author(s)
      Umezu T, Imanishi S, Azuma K, Kobayashi C, Ohyashiki K, Ohyashiki JH
    • Organizer
      10th AACR-JCA Joint Conference
    • Place of Presentation
      Maui, Hawaii
    • Year and Date
      2016-02-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Down-regulation of plasma miR-215 in chronic myeloid leukemia patients with successful imatinib discontinuation.2016

    • Author(s)
      Ohyashiki K, Umezu T, Katagiri S, Kobayashi C, Azuma K, Tauchi T, Okabe S, Fukuoka Y, Ohyashiki JH
    • Organizer
      10th AACR-JCA Joint Conference
    • Place of Presentation
      Maui, Hawaii
    • Year and Date
      2016-02-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Phase 1/2 study of WT1 peptide cancer vaccine WT4869 in patients with myelodysplastic syndromes (MDS).2015

    • Author(s)
      Suzuki T, Ohyashiki K
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [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
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] Exosomal miRNA signature of late onset acute GVHD in allogeneic HSCT.2015

    • Author(s)
      Yoshizawa S, Umezu T, Ohyashiki JH, Ohyashiki K
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [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
    • Related Report
      2015 Annual Research Report
  • [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, Ohyashiki JH, Ohyashiki K
    • Organizer
      20th European Hematology Association Congress
    • Place of Presentation
      Wien, Austria
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone marrow mesenchymal stromal cells from healthy donors secrete exosomes that inhit in vivo tumor growth and angiogenesis in multiple myeloma.2015

    • Author(s)
      Umezu T, Ohyashiki K, Ohyashiki JH
    • Organizer
      20th European Hematology Association Congress
    • Place of Presentation
      Wien, Austria
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The genome-wide DNA methylation status as a predictor of 5-azacytidine in clinical responses.2015

    • Author(s)
      Asao M, Kobayashi C, Umezu T, Ohyashiki K, Ohyashiki K
    • Organizer
      6th JSH International symposium
    • Place of Presentation
      軽井沢
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Age-related alterations in exosomal miRNAs derived from bone marrow mesenchymal stromal cells.2015

    • Author(s)
      Umezu T, Ohyashiki K, Ohyashiki JH
    • Organizer
      6th JSH International symposium
    • Place of Presentation
      軽井沢
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Book] 貧血学―最新の診断・治療動向―:MDS診療ガイドラインにおける治療戦略・概論2017

    • Author(s)
      大屋敷一馬
    • Total Pages
      641
    • Publisher
      日本臨牀社
    • Related Report
      2017 Annual Research Report
  • [Book] Chromosomes and chromosomal instability in human cancer. The Molecular Basis of Human Cancer (2nd Edition).2016

    • Author(s)
      Ohyashiki K, Kuroda M, Ohyashiki JH
    • Total Pages
      873
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] 内科学第10版2015

    • Author(s)
      大屋敷一馬
    • Total Pages
      2548
    • Publisher
      朝倉書店
    • Related Report
      2015 Annual Research Report
  • [Book] 入門腫瘍内科学(改訂第2版)2015

    • Author(s)
      大屋敷一馬、大屋敷純子
    • Total Pages
      234
    • Publisher
      篠原出版
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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