Immunogenetic factor responsible to GvH reaction and/or GvL reaction.

• Project Area: HLA polymorphism, disease and evolution
• Project/Area Number: 22133011
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: MORISHIMA Yasuo 愛知県がんセンター(研究所), 疫学・予防部, 研究員 (20220056)
• Co-Investigator(Kenkyū-buntansha): MORISHIMA Satoko 藤田保健衛生大学, 医学部, 講師 (40463195)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥54,990,000 (Direct Cost: ¥42,300,000、Indirect Cost: ¥12,690,000); Fiscal Year 2014: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000); Fiscal Year 2013: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000); Fiscal Year 2012: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000); Fiscal Year 2011: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000); Fiscal Year 2010: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000)
• Keywords: ＧＶＨＤ / ＧＶＬ効果 / ＨＬＡ / 造血幹細胞移植 / HLA / GVHD / ゲノム / 免疫学 / 移植

Outline of Final Research Achievements

Hematopoietic stem cell transplantation induces specific immunological reactions. Donor-derived immune cells attack patient tissues resulting in graft-versus-host disease (GVHD), and do patient leukemia cells in graft-versus-leukemia (GVL) effect. This study focused on these GVHD and GVL effect using large cohort of unrelated donor transplant with HLA data and clinical data. Refined immuno-genetic methods elucidated that the diversity of HLA antigen and their conservative segment of HLA region induces ordered degree of GVHD and GVL effect. These findings is important not only for clinical transplant but also for understanding the mechanism of transplant-related immunological reaction and auto-immune reaction.

Research Products

• [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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Significance of ethnicity in the risk of acute graft-versus-host disease and leukemia relapse after unrelated donor hematopoietic stem cell transplantation. (2013)
  • Author(s): Morishima Y, et al.
  • Journal Title: Biol Blood Marrow Transplant Volume: 19(8) Issue: 8 Pages: 1197-203
  • DOI: 10.1016/j.bbmt.2013.05.020
  • Peer Reviewed
• [Journal Article] Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation. (2013)
  • Author(s): Harkensee C, Morishima Y, et al.
  • Journal Title: Immunogenetics Volume: 65(6) Issue: 6 Pages: 417-27
  • DOI: 10.1007/s00251-013-0691-z
  • Peer Reviewed
• [Journal Article] GVHD、GVL効果におけるHLAの役割 (2013)
  • Author(s): 森島聡子、森島泰雄
  • Journal Title: 血液フロンティア Volume: 23(8) Pages: 1091-1098
• [Journal Article] Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation. (2013)
  • Author(s): Harkensee C
  • Journal Title: Immunogenetics Volume: in press
  • Peer Reviewed
• [Journal Article] Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation: an exploration study (2012)
  • Author(s): Harkensee C
  • Journal Title: Blood Volume: 119 Pages: 6365-6372
  • Peer Reviewed
• [Journal Article] 造血幹細胞移植におけるHLAハプロタイプの意義 (2012)
  • Author(s): 森島聡子
  • Journal Title: 医学のあゆみ Volume: 240 Pages: 478-484
• [Journal Article] Comparison of unrelated cord blood and HLA-mismatched unrelated bone marrow transplantation for adults with leukemia (2012)
  • Author(s): Atsuta Y.
  • Journal Title: Biol.Blood Marrow Transplant. Volume: 18(5) Pages: 780-787
  • Peer Reviewed
• [Journal Article] Frequent loss of HLA allele associated with copy number-neutral 6pLOH in acquired aplastic anemia (2011)
  • Author(s): Katagiri T.
  • Journal Title: Blood Volume: 118(25) Pages: 6601-6609
  • Peer Reviewed
• [Journal Article] Prediction in the face of clinical reality : HistoCheck versus high-risk HLA allele mismatch combinations responsible for severe GVHD (2011)
  • Author(s): Asker M.
  • Journal Title: Biol.Blood Marrow Transplant. Volume: 17(9) Pages: 1409-1415
  • Peer Reviewed
• [Journal Article] Impact of highly conserved HLA haplotype on acute graft-versus-host disease. (2010)
  • Author(s): Morishima S
  • Journal Title: Blood Volume: 115 Pages: 4664-4670
  • Peer Reviewed
• [Presentation] HLA適合血縁者間移植においてGVHDの発症は移植後白血病再発に影響を与えるか。 (2015)
  • Author(s): 森島泰雄、森島聡子、村田 誠、松尾恵太郎。諫田淳也、大橋一樹、福田隆浩、金森平和、吉田 均、熱田由子、一戸辰夫、神田善伸。
  • Organizer: 第27回日本造血細胞移植学会総会。
  • Place of Presentation: 神戸国際会議場 神戸市
  • Year and Date: 2015-03-06
• [Presentation] HLA matching and outcome of unrelated donor hematopoietic stem cell transplantation. (2014)
  • Author(s): Yasuo Morishima, Koichi Kashiwase, Keitaro Matsuo, Fumihiro Azuma, Satoko Morishima, Makoto Onizuka, Toshio Yabe, Makoto Murata, Noriko Doki, Tetsuya Eto, Takehiko Mori, Koichi Miyamura, Hiroshi Sao, Tatsuo Ichinohe, Hiroo Saji, Shunichi Kato, Yoshiko Atsuta, Keisei Kawa, Yoshihisa Kodera, Takehiko Sasazuki.
  • Organizer: The 19th Congress of the Asia-Pacific Blood and Marrow Transplantation.
  • Place of Presentation: Ｈａｎｇｚｈｏｕ Ｉｎｔｅｒｃｏｎｔｉｎｅｎｔａｌ Ｈｏｔｅｌ 中国
  • Year and Date: 2014-10-07
• [Presentation] 造血幹細胞移植におけるHLAハプロタイプの意義（シンポジウム） (2013)
  • Author(s): 森島聡子
  • Organizer: 第35回日本造血細胞移植学会
  • Place of Presentation: 金沢音楽堂（金沢）
  • Year and Date: 2013-03-09
• [Presentation] Impact of HLA and HLA haplotype on transplantation related immunological evevts as as artificial model of disease susseptability. (2012)
  • Author(s): Morishima Yasuo
  • Organizer: International Symposium. Autoimmune disease -Ethiology and Therapeutics.
  • Place of Presentation: ACROS Fukuoka (Fukuoka, Japan)
  • Year and Date: 2012-12-02
  • Invited
• [Presentation] The role of HLA and its matching for trenaplant-related immune response in unrelated hematopoietic stem cell transplantation. (2012)
  • Author(s): Morishima Yasuo
  • Organizer: 36th Asia-Pacific Histocompatibility and Immunogenetics Association
  • Place of Presentation: Convention Center (Adelaide, Australia)
  • Year and Date: 2012-11-17
  • Invited
• [Presentation] 非血縁者間骨髄移植におけるHLAハプロタイプの意義 (2012)
  • Author(s): 森島聡子
  • Organizer: 第21回日本組織適合性学会大会
  • Place of Presentation: 明治大学（東京）
  • Year and Date: 2012-09-15
• [Presentation] Multi-SNP analysis of HLA haplotype and its matching effect on hematopoietic stem cell transplantation from unrelated donor. (2012)
  • Author(s): Morishima Satoko
  • Organizer: 16th International HLA and Immunogenetics Workshop and Conference.
  • Place of Presentation: BT Convention Centre (Liverpool, UK)
  • Year and Date: 2012-06-01
• [Presentation] Impact of HLA on unrelated HSCT (2011)
  • Author(s): Morishima Y.
  • Organizer: 2^<nd> Chinese Blood and Marrow Transplantation Forum
  • Place of Presentation: Shangri-La Hotel Guilin, Guangxi, China
  • Year and Date: 2011-09-02
• [Presentation] Multi-SNP解析による日本人HLAハプロタイプの均一性の検討 (2010)
  • Author(s): 森島聡子
  • Organizer: 日本組織適合性学会
  • Place of Presentation: 東京大学(東京都)
  • Year and Date: 2010-09-18
• [Presentation] Impact of HLA allele and haplotype on acute graft-versus-host disease and survival in hematopoietic stem cell transplantation from unrelated donor.
  • Author(s): 1Morishima S, Kashiwase K, Azuma F, Yabe T, Sato-Otsubo A, Ogawa S, Shiina T, Satake M, Hiroo S, Kato S, Kodera Y, Sasazuki T, Morishima Y.
  • Organizer: 55th Annual Meeting of American Society of Hematology
  • Place of Presentation: Ernest N. Memorial Convention Center (New Orleans, USA)
• [Presentation] 同種造血幹細胞移植におけるHLAハプロタイプの意義.
  • Author(s): 森島聡子
  • Organizer: 第22回日本組織適合性学会大会シンポジウム
  • Place of Presentation: コラッセ福島（福島市）
• [Presentation] HLA一致同朋間移植におけるHLA型およびHLAハプロタイプが急性GVHDに及ぼす影響
  • Author(s): 森島聡子, 松尾恵太郎, 小林武, 森毅彦, 鬼塚真仁, 日高道弘, 福田隆浩, 井上雅美, 田中淳司, 熱田由子, 神田善伸, 森島泰雄
  • Organizer: 第36回日本造血細胞移植学会総会
  • Place of Presentation: 沖縄コンベンションセンター（宜野湾市）