Molecular analysis of donor cells of pre- and post- bone marrow transplantation for the analysis of the underlying mechanism of leukemia of donor cell origin

• Project/Area Number: 25461464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kurume University
• Principal Investigator: Nagafuji Koji 久留米大学, 医学部, 教授 (60343323)
• Co-Investigator(Kenkyū-buntansha): MIZUNO Shinichi 九州大学, 先端医療イノベーションセンター, 准教授 (40569430) ; 岡村 孝 久留米大学, 医学部, 教授 (30136436)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 造血幹細胞移植 / ドナー由来白血病 / 白血病再発 / 遺伝子解析

Outline of Final Research Achievements

The presence of leukemia that derived from donor cell origin, could support the possibility that recipient’s microenvironment of bone marrow under allogeneic immune reactions can be harmful to transplanted donor cells. To investigate the possible effects of recipient’s microenvironment for donor cells, we performed whole exome sequencing on donor cells of pre- and post- bone marrow transplantation. In addition, to find out targets of allogeneic immune response, we searched minor antigens by analyzing neo-peptides derived from non-synonymous SNPs. Although, we did not find out any acquired somatic mutations in donor cells after transplantation so far, we could detect around 200 SNPs that can be candidates for minor antigens in examined cases, and those minor antigens identification by each exome sequencing will be good targets for immunotherapy after bone marrow transplantation.

Research Products

• [Journal Article] GVHD after HLA-matched sibling BMT or PBSCT: Comparison of North American Caucasian and Japanese populations (2016)
  • Author(s): Kanda J, Brazauskas R, Hu Z, Kuwatsuka Y, Nagafuji K, Kanamori H, Kanda Y, Miyamura K, Murata M, Fukuda T, Sakamaki H, Kimura F, Seo S, Aljurf M, Yoshimi A, Milone G, Wood WA, Ustun C, Hashimi S, Pasquini M, Bonfim C, Dalal J, Hahn T, Atsuta Y, Saber W
  • Journal Title: Biol Blood Marrow Transplant Volume: 22 Issue: 4 Pages: 744-751
  • DOI: 10.1016/j.bbmt.2015.12.027
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Effects of conditioning intensity in allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. (2015)
  • Author(s): Takashima S, Miyamoto T, Kamimura T, Yoshimoto G, Yoshida S, Henzan H, Takase K, Kato K, Ito Y, Ohno Y, Nagafuji K, Eto T, Teshima T, Akashi K.
  • Journal Title: Int J Hematol. Volume: 102 Pages: 689-696
  • Peer Reviewed
• [Journal Article] Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. (2015)
  • Author(s): Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, Sugita Y, Yufu Y, Choi I, Abe Y, Uike N, Nagafuji K, Okamura T, Akashi K, Takayanagi R, Shiratsuchi M, Ohshima K.
  • Journal Title: Blood Volume: 126 Issue: 19 Pages: 2193-2201
  • DOI: 10.1182/blood-2015-02-629600
  • Peer Reviewed
• [Journal Article] Characteristics of patients with development of large granular lymphocyte expansion among dasatinib-treated patients with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia after allogeneic stem cell transplantation. (2015)
  • Author(s): Ito Y, Miyamoto T, Kamimura T, Aoki K, Henzan H, Aoki T, Shiratsuchi M, Kato K, Nagafuji K, Ogawa R, Eto T, Iwasaki H, Akashi K.
  • Journal Title: Clin Lymphoma Myeloma Leuk. Volume: 15 Issue: 3 Pages: 47-54
  • DOI: 10.1016/j.clml.2014.09.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning. (2014)
  • Author(s): Koyama M, Hashimoto D, Nagafuji K, Eto T, Ohno Y, Aoyama K, Iwasaki H, Miyamoto T, Hill GR, Akashi K, Teshima T.
  • Journal Title: Bone Marrow Transplant. Volume: 2014 Issue: 1 Pages: 110-115
  • DOI: 10.1038/bmt.2013.134
  • NAID: 120005460247
  • Peer Reviewed / Open Access
• [Journal Article] Association between thromboembolic events and the JAK2 V617F mutation in myeloproliferative neoplasms. (2014)
  • Author(s): Takata Y, Seki R, Kanajii T, Nohara M, Koteda S, Kawaguchi K, Nomura K, Nakamura T, Morishige S, Oku E, Osaki K, Hashiguchi E, Mouri F, Yoshimoto K, Nagafuji K, Okamura T.
  • Journal Title: Kurume Med J. Volume: 60 Pages: 89-97
  • NAID: 130004678851
  • Peer Reviewed
• [Journal Article] Donor-derived 47, XXY in an unrelated cord blood transplant recipient. (2014)
  • Author(s): Kawaguchi K, Nakamura T, Nohara M, Koteda S, Nomura K, Morishige S, Oku E, Imamura R, Mouri F, Seki R, Osaki K, Hashiguchi M, Yoshimoto K, Nagafuji K, Okamura T.
  • Journal Title: Springerplus. Volume: 6 Issue: 1 Pages: 72-72
  • DOI: 10.1186/2193-1801-3-72
  • Peer Reviewed
• [Journal Article] Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission (2013)
  • Author(s): Eto T, Takase K, Miyamoto T, Ohno Y, Kamimura T, Nagafuji K, Takamatsu Y, Teshima T, Gondo H, Taniguchi S, Akashi K, Harada M
  • Journal Title: Int J Hematol Volume: 98 Issue: 2 Pages: 186-196
  • DOI: 10.1007/s12185-013-1378-9
  • NAID: 10031194734
  • Peer Reviewed
• [Journal Article] Contribution of bone marrow-derived hematopoietic stem/progenitor cells to the generation of donor-marker(+) cardiomyocytes in vivo. (2013)
  • Author(s): Fukata M, Ishikawa F, Najima Y, Yamauchi T, Saito Y, Takenaka K, Miyawaki K, Shimazu H, Shimoda K, Kanemaru T, Nakamura K, Odashiro K, Nagafuji K, Harada M, Akashi K.
  • Journal Title: PLoS One Volume: 8 Issue: 5 Pages: e62506-e62506
  • DOI: 10.1371/journal.pone.0062506
  • Peer Reviewed
• [Journal Article] Monitoring of minimal residual disease (MRD) is useful to predict prognosis of adult patients with Ph-negative ALL : results of a prospective study (ALL MRD2002 Study) (2013)
  • Author(s): Nagafuji K, Miyamoto T, Eto T, Kamimura T, Taniguchi S, Okamura T, Ohtsuka E, Yoshida T, Higuchi M, Yoshimoto G, Fujisaki T, Abe Y, Takamatsu Y, Yokota S, Akashi K, Harada M. (16名, 6番目)
  • Journal Title: J Hematol Oncol Volume: 6 Issue: 1 Pages: 14-14
  • DOI: 10.1186/1756-8722-6-14
  • Peer Reviewed