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HLA haplotype effects in allogeneic hematopoietic stem cell transplantation

Research Project

Project/Area Number 26461455
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionUniversity of the Ryukyus (2016)
Fujita Health University (2014-2015)

Principal Investigator

MORISHIMA Satoko  琉球大学, 医学(系)研究科(研究院), 准教授 (40463195)

Co-Investigator(Kenkyū-buntansha) 森島 泰雄  愛知県がんセンター(研究所), その他部局等, 研究員 (20220056)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords同種造血幹細胞移植 / HLA / HLAハプロタイプ / 急性GVHD / 造血幹細胞移植
Outline of Final Research Achievements

We demonstrated the structure of Japanese common HLA haplotypes using multi-SNP data in HLA region of 1500 patient-donor unrelated bone marrow transplantation (UR-BMT) pairs.
We also identified high-risk HLA alleles and haplotypes for severe acute graft-versus-host disease (aGVHD) using database of 6967 UR-BMT pairs from the Japan Marrow Donor Program. The patient and/or donor HLA-B*51:01 and patient HLA-C*14:02 were significantly associated with an increased risk of severe aGVHD. Furthermore, patient mismatched HLA-C*14:02 showed the highest risk of severe aGVHD and overall mortality among all patient mismatched HLA-C alleles. KIR2DL-ligand mismatch has been considered as high-risk HLA-C mismatch in Japanese UR-BMT, however our data demonstrated that the effect of KIR2DL-ligand mismatch was attributable to patient HLA-C*14:02 and donor HLA-C*15:02 mismatch combination. Patient mismatched HLA-C*14:02 should be considered a non-permissive HLA-C mismatch in donor selection for UR-BMT.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (13 results)

All 2016 2015

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 4 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] High-risk HLA alleles for severe acute graft-versus-host disease and mortality in unrelated donor bone marrow transplantation.2016

    • Author(s)
      Morishima S, Kashiwase K, Matsuo K, Azuma F, Yabe T, Sato-Otsubo A, Ogawa S, Shiina T, Satake M, Saji H, Kato S, Kodera Y, Sasazuki T, Morishima Y.
    • Journal Title

      Haematologica

      Volume: 101 Issue: 4 Pages: 491-498

    • DOI

      10.3324/haematol.2015.136903

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gene Map of the HLA Region, Graves' Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation.2016

    • Author(s)
      Sasazuki T, Inoko H, Morishima S, Morishima Y.
    • Journal Title

      Adv Immunol

      Volume: 129 Pages: 175-249

    • DOI

      10.1016/bs.ai.2015.08.003

    • ISBN
      9780128047996
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 非血縁同種造血幹細胞移植におけるHLA-DPB1ミスマッチと急性移植片対宿主病(GVHD)2016

    • Author(s)
      森島聡子
    • Journal Title

      血液内科

      Volume: 72 Pages: 344-350

    • Related Report
      2015 Research-status Report
  • [Journal Article] Genome wide surveillance of mismatched alleles for graft versus host disease in stem cell transplantation.2015

    • Author(s)
      A. Sato-Otsubo, Y. Nannya, K. Kashiwase, M. Onizuka, F. Azuma, Y. Akatsuka, Y. Ogino, M. Satake, M. Sanada, S. Chiba, H. Saji, H. Inoko, G. C. Kennedy, K. Yamamoto, S. Morishima, Y. Morishima, Y. Kodera, T. Sasazuki, and S. Ogawa
    • Journal Title

      blood

      Volume: 126 Issue: 25 Pages: 2752-2763

    • DOI

      10.1182/blood-2015-03-630707

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cost-efficient multiplex PCR for routine genotyping of up to nine classical HLA loci in a single analytical run of multiple samples by next generation sequencing.2015

    • Author(s)
      Ozaki Y, Suzuki S, Kashiwase K, Shigenari A, Okudaira Y, Ito S, Masuya A, Azuma F, Yabe T, Morishima S, Mitsunaga S, Satake M, Ota M, Morishima Y, Kulski JK, Saito K, Inoko H, Shiina T.
    • Journal Title

      BMC Genomics

      Volume: 16 Issue: 1 Pages: 318-318

    • DOI

      10.1186/s12864-015-1514-4

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Increased T-cell responses to Epstein-Barr virus with high viral load in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.2015

    • Author(s)
      Morishima S, Nakamura S, Yamamoto K, Miyauchi H, Kagami Y, Kinoshita T, Onoda H, Yatabe Y, Ito M, Miyamura K, Nagai H, Moritani S, Sugiura I, Tsushita K, Mihara H, Ohbayashi K, Iba S, Emi N, Okamoto M, Iwata S, Kimura H, Kuzushima K, Morishima Y.
    • Journal Title

      Leuk Lymphoma.

      Volume: 56 Issue: 4 Pages: 1072-1078

    • DOI

      10.3109/10428194.2014.938326

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biological significance of HLA locus matching in unrelated donor bone marrow transplantation.2015

    • Author(s)
      Morishima Y, Kashiwase K, Matsuo K, Azuma F, Morishima S, Onizuka M, Yabe T, Murata M, Doki N, Eto T, Mori T, Miyamura K, Sao H, Ichinohe T, Saji H, Kato S, Atsuta Y, Kawa K, Kodera Y, Sasazuki T; Japan Marrow Donor Program.
    • Journal Title

      Blood

      Volume: 125 Issue: 7 Pages: 1189-1197

    • DOI

      10.1182/blood-2014-10-604785

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 急性GVHD発症に関与する系統樹に基づくHLA-DP2/DP5 groupの同定とHLA-DPB1 T-cell-epitope matchingとの関連2016

    • Author(s)
      森島聡子、椎名隆、小川誠司、鈴木進悟、柏瀬貢一、東史啓、屋部登志雄、佐治博夫、笹月健彦、森島泰雄
    • Organizer
      第25回日本組織適合性学会大会
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2016-10-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Evolutionary basis of HLA alleles affects acute GVHD in unrelated donor stem cell transplantation2016

    • Author(s)
      Morishima S, Shiina T, Ogawa S, Suzuki S, Sato-Otsubo A, Kashiwase K, Azuma F, Yabe T, Matsuo K, Saji H, Kodera Y, Sasazuki T, Morishima Y
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜 (神奈川県横浜市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 非血縁者間骨髄移植において重症急性GVHDのリスクが高いHLAアリルの同定2016

    • Author(s)
      森島聡子、柏瀬貢一、松尾恵太郎、東史啓、屋部登志雄、佐藤亜以子、小川誠司、椎名隆、佐竹正博、佐治博夫、加藤俊一、小寺良尚、笹月健彦、森島泰雄
    • Organizer
      第38回日本造血細胞移植学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2016-03-03
    • Related Report
      2015 Research-status Report
  • [Presentation] High risk HLA allele for severe acute graft-versus-host disease and mortality in unrelated donor hematopoietic stem cell transplantation.2016

    • Author(s)
      Morishima S, Kashiwase K, Matsuo K, Azuma F, Yabe T, Sato-Otsubo A, Ogawa S, Shiina T, Satake M, Saji H, Kato S, Kodera Y, Sasazuki T, Morishima Y.
    • Organizer
      BMT Tandem Meetings 2016
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of HLA-DPB1 T-cell-epitope matching in unrelated donor bone marrow transplantation: The Japan Marrow Donor Program analysis.2015

    • Author(s)
      Morishima S, Kashiwase K, Azuma F, Yabe T, Sasazuki T, Kodera Y, Morishima Y.
    • Organizer
      The 20th Annual Congress of Asia-Pacific Blood and Marrow Transplantation Group
    • Place of Presentation
      Okinawa, JAPAN
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 日本骨髄バンクの非血縁者間骨髄移植におけるHLA-DPB1 T-cell epitope matchingの影響2015

    • Author(s)
      森島聡子、柏瀬貢一、東史啓、屋部登志雄、笹月健彦、森島泰雄
    • Organizer
      第24回日本組織適合性学会大会
    • Place of Presentation
      ホテルレイクビュー水戸
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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