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

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659486
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kanazawa 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

• [Journal Article] Increased plasma thrombopoietin levels in patients with myelodysplastic syndrome: a reliable marker for a benign subset of bone marrow failure (2013)
  • 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 lineages (2013)
  • 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' designation (2012)
  • 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 anemia (2011)
  • 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 response (2011)
  • 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 pathophysiology (2012)
  • 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