Establishment of optimal hematopoietic stem cell transplantation donor selection based on analysis of immune-related gene polymorphism

• Project/Area Number: 21591236
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: TAKAMI Akiyoshi 金沢大学, 附属病院, 准教授 (80324078)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝子多型 / 免疫関連遺伝子 / 移植片対宿主病 / IL-17 / CXCL10 / Granzyme B / 同種造血幹細胞移植

Research Abstract

When the impact of immune-related gene polymorphisms was examined in patients and their donors of unrelated hematopoietic stem cell transplantation, genetic variations in the NKG2D, Granzyme B, CXCL10, NLRP3, FCGR3A, IL-17, and PTPN22 genes were associated with transplant outcomes. Experimental investigation revealed that the gene polymorphisms of NKG2D, IL-17 and CXCL10 play functionally important roles in the regulation of their production. These findings suggest that determination of such gene polymorphisms prior to transplantation offer clinical benefits in patients undergoing allogeneic hematopoietic stem cell transplantation

Research Products

• [Journal Article] Human microRNA-1245 downregulates the NKG2D receptor in NK cells and impairs NKG2D-mediated functions (2012)
  • Author(s): Espinoza JL, Takami A, (他5名)
  • Journal Title: Haematologica Volume: (in press) Issue: 9 Pages: 1295-303
  • DOI: 10.3324/haematol.2011.058529
  • Peer Reviewed
• [Journal Article] Prognostic factors for acute myeloid leukemia patients with t(6 ; 9)(p23 ; q34) who underwent an allogeneic hematopoietic stem cell transplant (2012)
  • Author(s): Ishiyama K, Takami A, (他11名)
  • Journal Title: Leukemia Volume: (in press) Issue: 6 Pages: 1416-9
  • DOI: 10.1038/leu.2011.350
  • Peer Reviewed
• [Journal Article] Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6 ; 9)(p23 ; q34) dramatically improves the patient prognosis : a matched-pair analysis (2012)
  • Author(s): Ishiyama K, Takami A, (他10名)
  • Journal Title: Leukemia Volume: (in press) Issue: 3 Pages: 461-464
  • DOI: 10.1038/leu.2011.229
  • Peer Reviewed
• [Journal Article] Intensive chemotherapy for a relapsed ALL patient who received living-donor lobar lung transplantation (2012)
  • Author(s): Ishiyama K, Takami A
  • Journal Title: Bone Marrow Transplant Volume: 47 Issue: 1 Pages: 135-6
  • DOI: 10.1038/bmt.2011.5
  • NAID: 120003989049
  • Peer Reviewed
• [Journal Article] Pulmonary Veno-occlusive Disease Following Reduced-intensity Allogeneic Bone Marrow Transplantation for Acute Myeloid Leukemia (2012)
  • Author(s): Hosokawa K, Takami A
  • Journal Title: Internal Medicine Volume: 51 Issue: 2 Pages: 195-198
  • DOI: 10.2169/internalmedicine.51.6302
  • NAID: 130002062063
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Successful treatment of Trichosporon fungemia in a patient with refractory acute myeloid leukemia using voriconazole combined with liposomal amphotericin B (2012)
  • Author(s): Hosokawa K, Takami A
  • Journal Title: Transplant Infect Dis Volume: (in press) Issue: 2 Pages: 184-187
  • DOI: 10.1111/j.1399-3062.2011.00670.x
  • NAID: 120003989036
  • Peer Reviewed
• [Journal Article] Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation (2012)
  • Author(s): Ishiyama K, Takami A
  • Journal Title: Transpl Infect Dis Volume: (in press) Issue: 1 Pages: 33-39
  • DOI: 10.1111/j.1399-3062.2011.00662.x
  • NAID: 120003989051
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT (2011)
  • Author(s): Espinoza JL, Takami A, (他13名)
  • Journal Title: Bone Marrow Transplant Volume: 46(11) Issue: 11 Pages: 1455-63
  • DOI: 10.1038/bmt.2010.325
  • Peer Reviewed
• [Journal Article] A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation (2011)
  • Author(s): Espinoza JL, Takami A, (他9名)
  • Journal Title: PLoS One Volume: 6(10) Issue: 10 Pages: e26229-e26229
  • DOI: 10.1371/journal.pone.0026229
  • Peer Reviewed
• [Journal Article] Genetic variants of human granzyme B predict transplant outcomes after HLA matched unrelated bone marrow transplantation for myeloid malignancies (2011)
  • Author(s): Espinoza LJ, Takami A, (他13名)
  • Journal Title: PLoS One Volume: 6(8) Issue: 8 Pages: e23827-e23827
  • DOI: 10.1371/journal.pone.0023827
  • Peer Reviewed
• [Journal Article] A single-nucleotide polymorphism of the Fcgamma receptor type IIIA gene in the recipient predicts transplant outcomes after HLA fully matched unrelated BMT for myeloid malignancies (2011)
  • Author(s): Takami A, (他15名)
  • Journal Title: Bone Marrow Transplant Volume: 46(2) Issue: 2 Pages: 238-43
  • DOI: 10.1038/bmt.2010.88
  • Peer Reviewed
• [Journal Article] Efficacy and safety of micafungin as an empirical therapy for invasive fungal infections in patients with hematologic disorders : a multicenter, prospective study (2011)
  • Author(s): Yamaguchi M, Takami A
  • Journal Title: Ann Hematol Volume: 90 Issue: 10 Pages: 1209-17
  • DOI: 10.1007/s00277-011-1277-1
  • Peer Reviewed
• [Journal Article] Use of mycophenolate mofetil in patients received allogeneic hematopoietic stem cell transplantation in Japan (2011)
  • Author(s): Iida M, Takami A
  • Journal Title: Int J Hematol Volume: 93 Issue: 4 Pages: 523-31
  • DOI: 10.1007/s12185-011-0817-8
  • NAID: 10029534696
  • Peer Reviewed
• [Journal Article] Intensive chemotherapy for a relapsed ALL patient who received living-donor lobar lung transplantation.Bone Marrow Transplant (2011)
  • Author(s): Ishiyama K, Takami A
  • Journal Title: Bone Marrow Transplant Volume: In press
  • Peer Reviewed
• [Journal Article] A single-nucleotide polymorphism of the Fcy receptor type IIIA gene in the recipient predicts transplant outcomes after HLA fully matched unrelated BMT for myeloid malignancies (2011)
  • Author(s): Takami A
  • Journal Title: Bone Marrow Transplant Volume: 46 Pages: 238-243
  • Peer Reviewed
• [Journal Article] Use of foscarnet for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation from a related donor (2010)
  • Author(s): Asakura M, Takami A
  • Journal Title: Int J Hematol Volume: 92 Pages: 351-359
  • NAID: 10026712482
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism of the Fc□ receptor type IIIA gene in the recipient predicts transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for myeloid malignancies (2010)
  • Author(s): Takami A
  • Journal Title: Bone Marrow Transplant (in press)
  • Peer Reviewed
• [Journal Article] NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies (2009)
  • Author(s): Espinoza JL, Takami A, (他12名)
  • Journal Title: Haematologica Volume: 94(10) Issue: 10 Pages: 1427-34
  • DOI: 10.3324/haematol.2009.008318
  • Peer Reviewed
• [Journal Article] Cord blood transplantation using minimum conditioning regimens for patients with hematologic malignancies complicated by severe infections (2009)
  • Author(s): Yamashita T, Takami A
  • Journal Title: Int J Hematol 89 Pages: 238-242
  • NAID: 10025160388
  • Peer Reviewed
• [Journal Article] Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome : a marker of karyotypic abnormalities associated with poor proenosis (2009)
  • Author(s): Sugimori N, Takami A
  • Journal Title: Eur J Haematol 82 Pages: 54-60
  • Peer Reviewed
• [Journal Article] Origin and fate of blood cells deficient in glycosylphosphatidylinositol-anchored protein among patients with bone marrow failure (2009)
  • Author(s): Sugimori C, Takami A
  • Journal Title: British Journal of Haematology 147 Pages: 102-112
  • Peer Reviewed
• [Journal Article] Relationship between tumor-infiltrating T lymphocytes and clinical response after reduced-intensity allogeneic hematopoietic stem cell transplantation for advanced renal cell carcinoma : a single center prospective study (2009)
  • Author(s): Ishiyama K, Takami A
  • Journal Title: Jpn J Clin Oncol 39 Pages: 807-812
  • Peer Reviewed
• [Journal Article] NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies (2009)
  • Author(s): Espinoza JL, Takami A
  • Journal Title: Haematologica 94 Pages: 1427-1434
  • Peer Reviewed
• [Presentation] Resveratrol Enhances NKG2D-Mediated Cytotoxicity Against Leukemia Cells by Upregulating Both NKG2D Receptor on NK Cells As Well As NKG2D Ligands on Target Cells (2011)
  • Author(s): Espinoza L, Takami A
  • Organizer: 米国血液学会
  • Place of Presentation: 国際会議場(米国)
  • Year and Date: 2011-12-12
• [Presentation] A Single Nucleotide Polymorphism in the NLRP3 Gene Is Associated with Acute Graft-Versus-Host Disease After HLA-Matched Unrelated Bone Marrow Transplantation (2011)
  • Author(s): Takami A, Espinoza L
  • Organizer: 米国血液学会
  • Place of Presentation: 国際会議場(米国)
  • Year and Date: 2011-12-12
• [Presentation] Resveratrol Enhances NKG2D-Mediated Cytotoxicity Against Leukemia Cells by Upregulating Both NKG2D Receptor on NK Cells As Well As NKG2D Ligands on Target Cells (2011)
  • Author(s): Espinoza L, Takami A
  • Organizer: アメリカ血液学会
  • Place of Presentation: 国際会議場(サンディエゴ)
  • Year and Date: 2011-12-12
• [Presentation] A Single Nucleotide Polymorphism in the NLRP3 Gene Is Associated with Acute Graft-Versus-Host Disease After HLA-Matched Unrelated Bone Marrow Transplantation (2011)
  • Author(s): Takami A, Espinoza L
  • Organizer: アメリカ血液学会
  • Place of Presentation: 国際会議場(サンディエゴ)
  • Year and Date: 2011-12-12
• [Presentation] A Sequence Variation in the Promoter Region of PTPN22 Gene Predicts Relapse After HLA-Fully-Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies (2011)
  • Author(s): Espinoza L, Takami A
  • Organizer: 米国血液学会
  • Place of Presentation: 国際会議場(米国)
  • Year and Date: 2011-12-11
• [Presentation] Prognostic Factors of Reducing Relapse in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation From Related Donor for Acute Myeloid Leukemia : The Japan Society for Hematopoietic Cell Transplantation(JSHCT) AML Working Group (2011)
  • Author(s): Yano S, Takami A
  • Organizer: 米国血液学会
  • Place of Presentation: 国際会議場(米国)
  • Year and Date: 2011-12-11
• [Presentation] A Sequence Variation in the Promoter Region of PTPN22 Gene Predicts Relapse After HLA-FuUy-Matched Unrelated Bone Marrow Transplantation for Hematologic Malignancies (2011)
  • Author(s): Espinoza L, Takami A
  • Organizer: アメリカ血液学会
  • Place of Presentation: 国際会議場(サンディエゴ)
  • Year and Date: 2011-12-11
• [Presentation] Prognostic Factors of Reducing Relapse in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation From Related Donor for Acute Myeloid Leukemia : The Japan Society for Hematopoietic Cell Transplantation (JSHCT) AML Working Group (2011)
  • Author(s): Yano S, Takami A
  • Organizer: アメリカ血液学会
  • Place of Presentation: 国際会議場(サンディエゴ)
  • Year and Date: 2011-12-11
• [Presentation] The Association of a Single Nucleotide Polymorphism in the Chemokine CXCL10 Gene with Transplant Outcomes After HLA-Matched Unrelated Bone Marrow Transplantation for Low Risk Hematologic Malignancies (2011)
  • Author(s): Nakata K, Takami A
  • Organizer: 米国血液学会
  • Place of Presentation: 国際会議場(米国)
  • Year and Date: 2011-12-10
• [Presentation] The Association of a Single Nucleotide Polymorphism in the Chemokine CXCL10 Gene with Transplant Outcomes After HLA-Matched Unrelated Bone Marrow Transplantation for Low Risk Hematologic Malignancies (2011)
  • Author(s): Nakata K, Takami A
  • Organizer: アメリカ血液学会
  • Place of Presentation: 国際会議場(サンディエゴ)
  • Year and Date: 2011-12-10
• [Presentation] 生着不全に対する再移植:One day regimenの試み (2011)
  • Author(s): 高見昭良
  • Organizer: 日本造血細胞移植学会
  • Place of Presentation: ひめぎんホール(松山市)
  • Year and Date: 2011-03-07
• [Presentation] A minor genetic variation in the Granzyme B gene predicts relapse after HLA-fully-matched unrelated bone marrow transplantation for hematologic malignancies (2010)
  • Author(s): Espinoza JL, Takami A
  • Organizer: 米国血液学会
  • Place of Presentation: 国際会議場(米国)
  • Year and Date: 2010-12-06
• [Presentation] Aminor genetic variation in the Granzyme B gene predicts relapse after HLA-funy-matched unrelated bone marrow transplantation for hemato logic malignancies (2010)
  • Author(s): Espinoza JL, Takami A
  • Organizer: アメリカ血液学会
  • Place of Presentation: 国際会議場(オーランド)
  • Year and Date: 2010-12-06
• [Presentation] A single nucleotide polymorphism of the Fcgamma receptor type IIIA gene in the recipient predicts transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for myeloid malignancies (2010)
  • Author(s): 高見昭良
  • Organizer: 欧州血液骨髄移植学会
  • Place of Presentation: コンベンションセンター (ウィーン)
  • Year and Date: 2010-03-22
• [Presentation] 輸血細胞療法・血液内科診療における自動血球分析の新たな展開 (2010)
  • Author(s): 高見昭良
  • Organizer: 石川県医学検査学会
  • Place of Presentation: 金沢大学附属病院 (金沢)
  • Year and Date: 2010-03-07
• [Presentation] ABOマイナー不適合非血縁者間骨髄移植後患者ABO抗原に対するIgM抗体の一過性産生 (2010)
  • Author(s): 高見昭良
  • Organizer: 日本造血細胞移植学会
  • Place of Presentation: アクトシティ浜松 (浜松)
  • Year and Date: 2010-02-18
• [Presentation] Significant Impact of IL-17A Gene Polymorphism On Transplant Outcomes After HLA-Fully-Matched Unrelated Bone Marrow Transplantation (2009)
  • Author(s): Takami A
  • Organizer: 米国血液学会
  • Place of Presentation: コンベンションセンター(米国)
  • Year and Date: 2009-12-07
• [Presentation] Significant Impact of IL-17A Gene Polymorphism On Transplant Outcomes After HLA-Fully-Matched Unrelated Bone Marrow Transplantation (2009)
  • Author(s): 高見昭良
  • Organizer: 米国血液学会
  • Place of Presentation: コンベンションセンター (ニューオーリンズ)
  • Year and Date: 2009-12-07
• [Presentation] IL-17A遺伝子多型はHLA一致非血縁者間骨髄移植成績に影響する (優秀ポスター賞) (2009)
  • Author(s): 高見昭良
  • Organizer: 日本血液学会
  • Place of Presentation: 京都国際会議場 (京都)
  • Year and Date: 2009-10-23
• [Presentation] 移植後再発に対するドナーリンパ球輸注の有用性 (2009)
  • Author(s): 高見昭良
  • Organizer: 日本アフェレーシス学会
  • Place of Presentation: 京王プラザホテル札幌 (札幌)
  • Year and Date: 2009-09-11