Establishment of tailor-made type allogeneic hematopoietic stem cell transplantation based on immune-modulating gene polymorphism analysis

• Project/Area Number: 24591418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Aichi Medical University (2013-2014); Kanazawa University (2012)
• Principal Investigator: TAKAMI Akiyoshi 愛知医科大学, 医学部, 教授 (80324078)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子多型 / 1塩基多型

Outline of Final Research Achievements

When the impact of immune-modulating gene polymorphisms was examined in patients and their donors of unrelated hematopoietic stem cell transplantation, genetic variations in the CXCL10, NLRP3, PTPN22, CD53, and THBD genes were associated with transplant outcomes. Experimental investigation revealed that the gene polymorphisms of NLRP3, CD53 and THBD play functionally important roles in the regulation of their production. These findings may offer clinical benefits in patients with receiving allogeneic hematopoietic stem cell transplants as well as those with autoimmune diseases, infectious diseases, cancers and receiving organ transplants.

Research Products

• [Journal Article] Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia cells. (2015)
  • Author(s): Sugimori N, Espinoza JL, Trung LQ, Takami A, Kondo Y, An DT, Sasaki M, Wakayama T, Nakao S.
  • Journal Title: PloS One Volume: - Issue: 4 Pages: e0120709-e0120709
  • DOI: 10.1371/journal.pone.0120709
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of continuous and twice-daily infusions of cyclosporine A for graft-versus-host-disease prophylaxis in pediatric hematopoietic stem cell transplantation (2014)
  • Author(s): 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
  • Journal Title: Pediatr Blood Cancer Volume: 62 Issue: 2 Pages: 291-98
  • DOI: 10.1002/pbc.25243
  • Peer Reviewed
• [Journal Article] 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)
  • Author(s): 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.
  • Journal Title: Biol Blood Marrow Transplant Volume: 20 Issue: 11 Pages: 1785-90
  • DOI: 10.1016/j.bbmt.2014.07.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two unrelated allogeneic bone marrow transplant recipients (2014)
  • Author(s): Mochizuki, K., Kondo, Y., Hosokawa, K., Ohata, K., Yamazaki, H., Takami, A., Sasaki, M., Sato, Y., Nakanuma, Y. and Nakao, S.
  • Journal Title: Intern Med Volume: 53 Pages: 499-503
  • NAID: 130003392679
  • Peer Reviewed
• [Journal Article] Decision analysis for donor selection in stem cell transplantation-HLA-8/8 allele-matched unrelated donor vs HLA-1 AG mismatched related donor (2014)
  • Author(s): 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.
  • Journal Title: Blood Cancer J Volume: 4 Issue: 12 Pages: e263-e263
  • DOI: 10.1038/bcj.2014.85
  • Peer Reviewed / Open Access
• [Journal Article] Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation. (2014)
  • Author(s): Hosokawa K, Yamazaki H, Nakamura T, Yoroidaka T, Imi T, Shima Y, Ohata K, Takamatsu H, Kotani T, Kondo Y, Takami A, Nakao S.
  • Journal Title: Transp Infectious Dis Volume: 16 Issue: 5 Pages: 843-846
  • DOI: 10.1111/tid.12266
  • Peer Reviewed / Open Access
• [Journal Article] 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)
  • Author(s): 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.
  • Journal Title: Transp Infectious Dis Volume: 16 Issue: 3 Pages: 412-420
  • DOI: 10.1111/tid.12224
  • Peer Reviewed / Open Access
• [Journal Article] Increased glycosylphosphatidylinositol-anchored protein-deficient granulocytes define a benign subset of bone marrow failures in patients with trisomy 8. (2014)
  • Author(s): Hosokawa K, Sugimori N, Katagiri T, Sasaki Y, Saito C, Seiki Y, Mochizuki K, Yamazaki H, Takami A, Nakao S.
  • Journal Title: Eur J Haemat Volume: 18 Issue: 3 Pages: 230-238
  • DOI: 10.1111/ejh.12484
  • NAID: 120005661927
  • Peer Reviewed / Open Access
• [Journal Article] Outcome of allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with central nervous system involvement (2014)
  • Author(s): 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.
  • Journal Title: Biol Blood Marrow Transplant Volume: 20 Issue: 12 Pages: 2029-33
  • DOI: 10.1016/j.bbmt.2014.09.001
  • Peer Reviewed
• [Journal Article] Adenovirus pneumonia presenting with nodular shadows on chest X-ray in two unrelated allogeneic bone marrow transplant recipients. (2014)
  • Author(s): Mochizuki K, Kondo Y, Hosokawa K, Ohata K, Yamazaki H, Takami A, Sasaki M, Sato Y, Nakanuma Y, Nakao S.
  • Journal Title: Intern Med. Volume: 53 Pages: 499-50
  • NAID: 130003392679
  • Peer Reviewed
• [Journal Article] Guest editorial: new basic and clinical aspects of graft-versus-host disease: what can we do without "Doc" Brown's help? (2013)
  • Author(s): Takami A.
  • Journal Title: Int J Hematol. Volume: 98 Pages: 273-274
  • Peer Reviewed
• [Journal Article] The role of non-HLA gene polymorphisms in graft-versus-host disease. (2013)
  • Author(s): Takami A.
  • Journal Title: Int J Hematol. 2013 Sep;98(3):309-18. doi: 10.1007/s12185-013-1416-7. Epub 2013 Aug 15. Volume: 98 Pages: 309-318
  • Peer Reviewed
• [Journal Article] IgM anti-recipient ABO antibodies predict acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. (2013)
  • Author(s): Zaimoku Y, Takami A, Sato H, Utsumi M, Nakao S.
  • Journal Title: Int J Hematol. Volume: 98 Issue: 1 Pages: 96-101
  • DOI: 10.1007/s12185-013-1360-6
  • NAID: 10031189601
  • Peer Reviewed
• [Journal Article] Ataxia-telangiectasia mutated kinase-mediated upregulation of NKG2D ligands on leukemia cells by resveratrol results in enhanced natural killer cell susceptibility. (2013)
  • Author(s): Luis Espinoza J, Takami A, Trung LQ, Nakao S.
  • Journal Title: Cancer Sci. 2 Volume: 104 Issue: 6 Pages: 657-662
  • DOI: 10.1111/cas.12141
  • NAID: 120005830596
  • Peer Reviewed
• [Journal Article] The recipient CXCL10 + 1642C>G variation predicts survival outcomes after HLA fully matched unrelated bone marrow transplantation (2013)
  • Author(s): Nakata, K., Takami, A et al
  • Journal Title: Clin Immunol Volume: 146 Issue: 2 Pages: 104-11
  • DOI: 10.1016/j.clim.2012.11.009
  • Peer Reviewed
• [Journal Article] Recipient PTPN22 -1123 C/C genotype predicts acute graft-versus-host disease after HLA fully matched unrelated bone marrow transplantation for hematologic malignancies (2013)
  • Author(s): Espinoza, J. L., Takami, A et al
  • Journal Title: Biol Blood Marrow Transplant Volume: 19 Issue: 2 Pages: 240-6
  • DOI: 10.1016/j.bbmt.2012.09.014
  • 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] 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
• [Presentation] 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)
  • Author(s): Takagi, Shinsuke, Masuoka, Kazuhiro, Uchida, Naoyuki, Kurokawa, Mineo, Nakamae, Hirohisa, Tsudo, Mitsuru, Iwato, Koji, Ichinohe, Tatsuo, Atsuta, Yoshiko and Takami, Akiyoshi
  • Organizer: ASH 2014
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] Thrombomodulin Has a Significant Impact on Transplant Outcomes after HLA-Fully-Matched Unrelated Bone Marrow Transplantation for Standard Risk Hematologic Malignancies (2014)
  • Author(s): 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
  • Organizer: ASH 2014
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] 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)
  • Author(s): 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
  • Organizer: ASH 2014
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] The Effects of the Repeated Administration of Resveratrol Monomer and Resveratrol Dimer on Circulating Immune Cells in Healthy Individuals (2014)
  • Author(s): Espinoza, Luis J., Trung, Ly Quoc, Yoshida, Akiyo, Yamada, Kayoko, Nakao, Shinji and Takami, Akiyoshi
  • Organizer: ASH 2014
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] A Genetic Variant in the CD53 Gene Is Associated with Clinical Outcomes after Unrelated Bone Marrow Transplantation (2014)
  • Author(s): Espinoza, Luis Jorge, Matsuo, Keitaro, Toda, Saki, Morishima, Yasuo, Onizuka, Makoto, Kashiwase, Koichi, Fukuda, Takahiro, Kodera, Yoshihisa, Nakao, Shinji and Takami, Akiyoshi
  • Organizer: ASH 2014
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] 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)
  • Author(s): Yokoyama, Hiroki Uchida, Naoyuki Kakihana, Kazuhiko Fukuda, Takahiro Kanamori, Heiwa Ogawa, Hiroyasu Nagamura, Tokiko Tanaka, Junji Morishima, Yasuo Atsuta, Yoshiko Takami, Akiyoshi
  • Organizer: American Society of Hematology (ASH) 55th Annual Meeting
  • Place of Presentation: New Orleans, Louisiana
• [Presentation] 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)
  • Author(s): Kanamori, H,Takami, A et al
  • Organizer: ASH Annual Meeting
  • Place of Presentation: Georgia World Congress Center (USA)
• [Presentation] Association of Functional Single Nucleotide Variation in the NLRP3 Gene with Survival Outcomes After Unrelated Bone Marrow Transplantation (2012)
  • Author(s): Takami, A et al
  • Organizer: ASH Annual Meeting
  • Place of Presentation: Georgia World Congress Center (USA)
• [Presentation] Resveratrol Induces Cell Cycle Arrest and Apoptosis in Malignant NK Cells Via JAK2/STAT3 Pathway Inhibition (2012)
  • Author(s): Quoc, TL, Takami, A et al
  • Organizer: ASH Annual Meeting
  • Place of Presentation: Georgia World Congress Center (USA)
• [Presentation] 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)
  • Author(s): Yamashita, T, Takami, A et al
  • Organizer: ASH Annual Meeting
  • Place of Presentation: Georgia World Congress Center (USA)