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2012 Fiscal Year Final Research Report

Identification of auto-antigens in acquired aplastic anemia associated with clonal hematopoiesis by hematopoietic stem cells with uniparental disomy of chromosome 6p

Research Project

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Project/Area Number 23659486
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKanazawa University

Principal Investigator

NAKAO Shinji  金沢大学, 医学系, 教授 (70217660)

Co-Investigator(Kenkyū-buntansha) AKATSUKA Yoshiki  藤田保健衛生大学, 医学部, 准教授 (70333391)
Project Period (FY) 2011 – 2012
Keywords再生不良性貧血 / 6pLOH / 自己抗原 / CLT / HLA-B*40:02
Research Abstract

To determine the exact prevalence of HLA-A allele-lacking leukocytes (HLA-LLs) in patients with acquired aplastic anemia (AA), we improved the sensitivity of flow cytometry and examined peripheral blood leukocytes of patients with newly-diagnosed AA patients. HLA-LLs were detectable in 6 (28.6%) of 21 patients who were heterozygous with the HLA-A allele. The percentage of HLA-A allele-lacking granulocytes in the total granulocytes ranged from 3.9% to 61.1% (median 8.4%), which was lower than that in patients in remission after immunosuppressive therapy. Cytotoxic T cell (CTL) clones (A6) were successfully established from one of the patients possessing HLA-LLs by stimulating patient’s CD8+T cells with K562 cells transfected with HLA-B*40:02 gene. A6 CTL killed K562 in B*40:02 restricted manner but did not kill other cells including EB virus-transformed lymphoblastoid cell line and Jurkat T cell line transduced with B*40:02.

  • Research Products

    (8 results)

All 2013 2012 2011

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (2 results)

  • [Journal Article] Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure2013

    • Author(s)
      Seiki Y., Sasaki Y., Hosokawa K., Saito C., Sugimori N., Yamazaki H., Takami A., Nakao S
    • Journal Title

      Haematologica

      Volume: 98(in press)

    • DOI

      DOI:10.3324/haematol.2012.066217

    • Peer Reviewed
  • [Journal Article] Individual hematopoietic stem cells in human bone marrow of patients with aplastic anemia or myelodysplastic syndrome stably give rise to limited cell lineages2013

    • Author(s)
      Katagiri T., Kawamoto H., Nakakuki T., Ishiyama K., Okada-Hatakeyama M., Ohtake S., Seiki Y., Hosokawa K., Nakao S.
    • Journal Title

      Stem Cells

      Volume: 31 Pages: 536-46

    • DOI

      DOI:10.1002/stem.1301.

    • Peer Reviewed
  • [Journal Article] Favorable outcome of patients who have 13q deletion: a suggestion for revision of the WHO 'MDS- U' designation2012

    • Author(s)
      Hosokawa K., Katagiri T., Sugimori N., Ishiyama K., Sasaki Y., Seiki Y., Sato-Otsubo A., Sanada M., Ogawa S., Nakao S.
    • Journal Title

      Haematologica

      Volume: 97 Pages: 1845-9

    • DOI

      DOI:10.3324/haematol.2011.061127

    • Peer Reviewed
  • [Journal Article] An Epstein-Barr virus-associated leukemic lymphoma in a patient treated with rabbit antithymocyte globulin and cyclosporine for hepatitis-associated aplastic anemia.2011

    • Author(s)
      Ohata K., Iwaki N., Kotani T., Kondo Y., Yamazaki H., Nakao S
    • Journal Title

      Acta Haematol

      Volume: 127 Pages: 96-99

    • DOI

      DOI:10.1159/000333609

    • Peer Reviewed
  • [Journal Article] Frequent loss of HLA alleles associated with copy number-neutral 6pLOH in acquired aplastic anemia2011

    • Author(s)
      Katagiri T., Sato-Otsubo A., Kashiwase K.,Morishima S., Sato Y., Mori Y., Kato M., Sanada M., Morishima Y., Hosokawa K., Sasaki Y., Ohtake S., Ogawa S., Nakao S
    • Journal Title

      Blood

      Volume: 118 Pages: 6601-6609

    • DOI

      DOI:10.1182/blood-2011-07-365189

    • Peer Reviewed
  • [Journal Article] Aplastic anemia successfully treated with rituximab: the possible role of aplastic anemia-associated autoantibodies as a marker for response2011

    • Author(s)
      Takamatsu H., Yagasaki H., Takahashi Y., Hama A., Saikawa Y., Yachie A., Koizumi S., Kojima S., Nakao S
    • Journal Title

      Eur J Haematol

      Volume: 86 Pages: 541-545

    • DOI

      DOI:10.1111/j.1600-0609.2011.01612.x

    • Peer Reviewed
  • [Presentation] SLIT1 mutation in patients with acquired aplastic anemia: Its relevance in immune pathophysiology2012

    • Author(s)
      Chizuru Saito
    • Organizer
      The American Society of Hematology 54th Annual Meeting
    • Place of Presentation
      GEORGIA WORLD CONGRESS CENTER Atlanta,Georgia, USA
    • Year and Date
      2012-12-10
  • [Presentation] Frequent loss of HLA alleles from hematopoietic stem cells in patients with hepatitis-associated aplastic anemia.2011

    • Author(s)
      Takamasa Katagiri
    • Organizer
      The American Society of Hematology 53rd Annual Meeting
    • Place of Presentation
      San Diego Convention Center, California, USA.
    • Year and Date
      2011-12-12

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Published: 2014-09-25  

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