免疫調整遺伝子多型解析に基づくテーラーメード型同種造血幹細胞移植の確立

• 研究課題/領域番号: 24591418
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 血液内科学
• 研究機関: 愛知医科大学 (2013-2014); 金沢大学 (2012)
• 研究代表者: 高見 昭良 愛知医科大学, 医学部, 教授 (80324078)
• 研究期間 (年度): 2012-04-01 – 2015-03-31
• 研究課題ステータス: 完了 (2014年度)
• 配分額: 5,330千円 (直接経費: 4,100千円、間接経費: 1,230千円); 2014年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2013年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2012年度: 2,210千円 (直接経費: 1,700千円、間接経費: 510千円)
• キーワード: 遺伝子多型 / 1塩基多型

研究成果の概要

免疫調整遺伝子多型を臨床的・機能的に解析し、CXCL10、NLRP3、PTPN22、CD53、THBD各遺伝子多型が、非血縁者間骨髄移植後転帰に影響すること、NLRP3、CD53、THBDが機能的多型であることを明らかにした。これらは、同種造血幹細胞移植にとどまらず、自己免疫疾患や感染症、がん、臓器移植診療への波及効果も期待される。

研究成果

• [雑誌論文] Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia cells. (2015)
  • 著者名/発表者名: Sugimori N, Espinoza JL, Trung LQ, Takami A, Kondo Y, An DT, Sasaki M, Wakayama T, Nakao S.
  • 雑誌名: PloS One 巻: - 号: 4 ページ: e0120709-e0120709
  • DOI: 10.1371/journal.pone.0120709
  • 査読あり / オープンアクセス
• [雑誌論文] Comparison of continuous and twice-daily infusions of cyclosporine A for graft-versus-host-disease prophylaxis in pediatric hematopoietic stem cell transplantation (2014)
  • 著者名/発表者名: Umeda, K., Adachi, S., Tanaka, S., Ogawa, A., Hatakeyama, N., Kudo, K., Sakata, N., Igarashi, S., Ohshima, K., Hyakuna, N., Chin, M., Goto, H., Takahashi, Y., Azuma, E., Koh, K., Sawada, A., Kato, K., Inoue, M., Atsuta, Y., Takami, A., Murata, M
  • 雑誌名: Pediatr Blood Cancer 巻: 62 号: 2 ページ: 291-98
  • DOI: 10.1002/pbc.25243
  • 査読あり
• [雑誌論文] Donor lymphocyte infusion for the treatment of relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation (2014)
  • 著者名/発表者名: Takami, A., Yano, S., Yokoyama, H., Kuwatsuka, Y., Yamaguchi, T., Kanda, Y., Morishima, Y., Fukuda, T., Miyazaki, Y., Nakamae, H., Tanaka, J., Atsuta, Y. and Kanamori, H.
  • 雑誌名: Biol Blood Marrow Transplant 巻: 20 号: 11 ページ: 1785-90
  • DOI: 10.1016/j.bbmt.2014.07.010
  • 査読あり / 謝辞記載あり
• [雑誌論文] Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two unrelated allogeneic bone marrow transplant recipients (2014)
  • 著者名/発表者名: Mochizuki, K., Kondo, Y., Hosokawa, K., Ohata, K., Yamazaki, H., Takami, A., Sasaki, M., Sato, Y., Nakanuma, Y. and Nakao, S.
  • 雑誌名: Intern Med 巻: 53 ページ: 499-503
  • NAID: 130003392679
  • 査読あり
• [雑誌論文] Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor (2014)
  • 著者名/発表者名: Kanda, J., Fuji, S., Kato, S., Takami, A., Tanaka, J., Miyamura, K., Ohashi, K., Fukuda, T., Ozawa, Y., Kanamori, H., Eto, T., Kobayashi, N., Iwato, K., Morishima, Y., Sakamaki, H., Atsuta, Y., Kanda, Y.
  • 雑誌名: Blood Cancer J 巻: 4 号: 12 ページ: e263-e263
  • DOI: 10.1038/bcj.2014.85
  • 査読あり / オープンアクセス
• [雑誌論文] Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation. (2014)
  • 著者名/発表者名: Hosokawa K, Yamazaki H, Nakamura T, Yoroidaka T, Imi T, Shima Y, Ohata K, Takamatsu H, Kotani T, Kondo Y, Takami A, Nakao S.
  • 雑誌名: Transp Infectious Dis 巻: 16 号: 5 ページ: 843-846
  • DOI: 10.1111/tid.12266
  • 査読あり / オープンアクセス
• [雑誌論文] Relative incidences and outcomes of Clostridium difficile infection following transplantation of unrelated cord blood, unrelated bone marrow, and related peripheral blood in adult patients: a single institute study. (2014)
  • 著者名/発表者名: Hosokawa K, Takami A, Tsuji M, Araoka H, Ishiwata K, Takagi S, Yamamoto H, Asano-Mori Y, Matsuno N, Uchida N, Masuoka K, Wake A, Makino S, Yoneyama A, Nakao S, Taniguchi S.
  • 雑誌名: Transp Infectious Dis 巻: 16 号: 3 ページ: 412-420
  • DOI: 10.1111/tid.12224
  • 査読あり / オープンアクセス
• [雑誌論文] Increased glycosylphosphatidylinositol-anchored protein-deficient granulocytes define a benign subset of bone marrow failures in patients with trisomy 8. (2014)
  • 著者名/発表者名: Hosokawa K, Sugimori N, Katagiri T, Sasaki Y, Saito C, Seiki Y, Mochizuki K, Yamazaki H, Takami A, Nakao S.
  • 雑誌名: Eur J Haemat 巻: 18 号: 3 ページ: 230-238
  • DOI: 10.1111/ejh.12484
  • NAID: 120005661927
  • 査読あり / オープンアクセス
• [雑誌論文] Outcome of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with central nervous system involvement (2014)
  • 著者名/発表者名: Aoki, J., Ishiyama, K., Taniguchi, S., Fukuda, T., Ohashi, K., Ogawa, H., Kanamori, H., Eto, T., Iwato, K., Sakamaki, H., Morishima, Y., Nagamura, T., Atsuta, Y. and Takami, A.
  • 雑誌名: Biol Blood Marrow Transplant 巻: 20 号: 12 ページ: 2029-33
  • DOI: 10.1016/j.bbmt.2014.09.001
  • 査読あり
• [雑誌論文] Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two unrelated allogeneic bone marrow transplant recipients. (2014)
  • 著者名/発表者名: Mochizuki K, Kondo Y, Hosokawa K, Ohata K, Yamazaki H, Takami A, Sasaki M, Sato Y, Nakanuma Y, Nakao S.
  • 雑誌名: Intern Med. 巻: 53 ページ: 499-50
  • NAID: 130003392679
  • 査読あり
• [雑誌論文] Guest editorial: new basic and clinical aspects of graft-versus-host disease: what can we do without "Doc" Brown's help? (2013)
  • 著者名/発表者名: Takami A.
  • 雑誌名: Int J Hematol. 巻: 98 ページ: 273-274
  • 査読あり
• [雑誌論文] The role of non-HLA gene polymorphisms in graft-versus-host disease. (2013)
  • 著者名/発表者名: Takami A.
  • 雑誌名: Int J Hematol. 2013 Sep;98(3):309-18. doi: 10.1007/s12185-013-1416-7. Epub 2013 Aug 15. 巻: 98 ページ: 309-318
  • 査読あり
• [雑誌論文] IgM anti-recipient ABO antibodies predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. (2013)
  • 著者名/発表者名: Zaimoku Y, Takami A, Sato H, Utsumi M, Nakao S.
  • 雑誌名: Int J Hematol. 巻: 98 号: 1 ページ: 96-101
  • DOI: 10.1007/s12185-013-1360-6
  • NAID: 10031189601
  • 査読あり
• [雑誌論文] Ataxia-telangiectasia mutated kinase-mediated upregulation of NKG2D ligands on leukemia cells by resveratrol results in enhanced natural killer cell susceptibility. (2013)
  • 著者名/発表者名: Luis Espinoza J, Takami A, Trung LQ, Nakao S.
  • 雑誌名: Cancer Sci. 2 巻: 104 号: 6 ページ: 657-662
  • DOI: 10.1111/cas.12141
  • NAID: 120005830596
  • 査読あり
• [雑誌論文] The recipient CXCL10 + 1642C>G variation predicts survival outcomes after HLA fully matched unrelated bone marrow transplantation (2013)
  • 著者名/発表者名: Nakata, K., Takami, A et al
  • 雑誌名: Clin Immunol 巻: 146 号: 2 ページ: 104-11
  • DOI: 10.1016/j.clim.2012.11.009
  • 査読あり
• [雑誌論文] Recipient PTPN22 -1123 C/C genotype predicts acute graft-versus-host disease after HLA fully matched unrelated bone marrow transplantation for hematologic malignancies (2013)
  • 著者名/発表者名: Espinoza, J. L., Takami, A et al
  • 雑誌名: Biol Blood Marrow Transplant 巻: 19 号: 2 ページ: 240-6
  • DOI: 10.1016/j.bbmt.2012.09.014
  • 査読あり
• [雑誌論文] Prognostic factors for acute myeloid leukemia patients with t(6 ; 9)(p23 ; q34) who underwent an allogeneic hematopoietic stem cell transplant (2012)
  • 著者名/発表者名: Ishiyama K, Takami A, (他11名)
  • 雑誌名: Leukemia 巻: (in press) 号: 6 ページ: 1416-9
  • DOI: 10.1038/leu.2011.350
  • 査読あり
• [雑誌論文] Human microRNA-1245 downregulates the NKG2D receptor in NK cells and impairs NKG2D-mediated functions (2012)
  • 著者名/発表者名: Espinoza JL, Takami A, (他5名)
  • 雑誌名: Haematologica 巻: (in press) 号: 9 ページ: 1295-303
  • DOI: 10.3324/haematol.2011.058529
  • 査読あり
• [学会発表] Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia Transformed from Ph-Negative Myeloproliferative Neoplasm: A Study from the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) (2014)
  • 著者名/発表者名: Takagi, Shinsuke, Masuoka, Kazuhiro, Uchida, Naoyuki, Kurokawa, Mineo, Nakamae, Hirohisa, Tsudo, Mitsuru, Iwato, Koji, Ichinohe, Tatsuo, Atsuta, Yoshiko and Takami, Akiyoshi
  • 学会等名: ASH 2014
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-06 – 2014-12-09
• [学会発表] Thrombomodulin Has a Significant Impact on Transplant Outcomes after HLA-Fully-Matched Unrelated Bone Marrow Transplantation for Standard Risk Hematologic Malignancies (2014)
  • 著者名/発表者名: Nomoto, Haruka, Morishita, Eriko, Takami, Akiyoshi, Katsu, Shiori, Yamaguchi, Daisuke, Morishima, Yasuo, Onizuka, Makoto, Kashiwase, Koichi, Fukuda, Takahiro, Kodera, Yoshihisa, Nakao, Shinji and Ohtake, Shigeki
  • 学会等名: ASH 2014
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-06 – 2014-12-09
• [学会発表] Comparable Leukemia-Free Survival after Autologous Hematopoietic Cell Transplantation Versus HLA-Identical Sibling Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia in First Complete Remission: A Registry Study By JSHCT (2014)
  • 著者名/発表者名: Mizutani, Motonori, Hara, Masahiko, Fujita, Hiroyuki, Aoki, Jun, Kanamori, Heiwa, Machida, Shinichiro, Yamasaki, Satoshi, Ohashi, Kazuteru, Usuki, Kensuke, Fukuda, Takahiro, Chou, Takaaki, Tanaka, Junji, Atsuta, Yoshiko and Takami, Akiyoshi
  • 学会等名: ASH 2014
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-06 – 2014-12-09
• [学会発表] The Effects of the Repeated Administration of Resveratrol Monomer and Resveratrol Dimer on Circulating Immune Cells in Healthy Individuals (2014)
  • 著者名/発表者名: Espinoza, Luis J., Trung, Ly Quoc, Yoshida, Akiyo, Yamada, Kayoko, Nakao, Shinji and Takami, Akiyoshi
  • 学会等名: ASH 2014
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-06 – 2014-12-09
• [学会発表] A Genetic Variant in the CD53 Gene Is Associated with Clinical Outcomes after Unrelated Bone Marrow Transplantation (2014)
  • 著者名/発表者名: Espinoza, Luis Jorge, Matsuo, Keitaro, Toda, Saki, Morishima, Yasuo, Onizuka, Makoto, Kashiwase, Koichi, Fukuda, Takahiro, Kodera, Yoshihisa, Nakao, Shinji and Takami, Akiyoshi
  • 学会等名: ASH 2014
  • 発表場所: San Francisco, USA
  • 年月日: 2014-12-06 – 2014-12-09
• [学会発表] Influence Of Donor Source On Relapse and Survival In Patients With Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Analysis From The Japan Society For Hematopoietic Cell Transplantation (JSHCT) AML Working Group (2013)
  • 著者名/発表者名: Yokoyama, Hiroki Uchida, Naoyuki Kakihana, Kazuhiko Fukuda, Takahiro Kanamori, Heiwa Ogawa, Hiroyasu Nagamura, Tokiko Tanaka, Junji Morishima, Yasuo Atsuta, Yoshiko Takami, Akiyoshi
  • 学会等名: American Society of Hematology (ASH) 55th Annual Meeting
  • 発表場所: New Orleans, Louisiana
• [学会発表] Outcome and Prognostic Index for Reduced-Intensity Allogeneic Stem Cell Transplantation (RIST) for Elderly Patients with De Novo Acute Myeloid Leukemia (AML): A Study From the AML Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) (2012)
  • 著者名/発表者名: Kanamori, H,Takami, A et al
  • 学会等名: ASH Annual Meeting
  • 発表場所: Georgia World Congress Center (USA)
• [学会発表] Association of Functional Single Nucleotide Variation in the NLRP3 Gene with Survival Outcomes After Unrelated Bone Marrow Transplantation (2012)
  • 著者名/発表者名: Takami, A et al
  • 学会等名: ASH Annual Meeting
  • 発表場所: Georgia World Congress Center (USA)
• [学会発表] Resveratrol Induces Cell Cycle Arrest and Apoptosis in Malignant NK Cells Via JAK2/STAT3 Pathway Inhibition (2012)
  • 著者名/発表者名: Quoc, TL, Takami, A et al
  • 学会等名: ASH Annual Meeting
  • 発表場所: Georgia World Congress Center (USA)
• [学会発表] Intravenous Busulfan-Based Myeloablative Conditioning Is Comparable to TBI-Based Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Recipients with Acute Myeloid Leukemia: A Nationwide Retrospective Study From the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation (2012)
  • 著者名/発表者名: Yamashita, T, Takami, A et al
  • 学会等名: ASH Annual Meeting
  • 発表場所: Georgia World Congress Center (USA)