| Project/Area Number |
24390243
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kanazawa University |
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Principal Investigator |
NAKAO Shinji 金沢大学, 医学系, 教授 (70217660)
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| Co-Investigator(Kenkyū-buntansha) |
AKATSUKA Yoshiki 藤田保健衛生大学, 医学部, 教授 (70333391)
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUI Hirotaka 広島大学, 原爆放射線医科学研究所, 准教授 (60379849)
TAKAMATSU Hiroyuki 金沢大学, 医学系, 助教 (70401932)
NISHIUCHI Takumi 金沢大学, 学際科学実験センター, 准教授 (20334790)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2014: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Keywords | 再生不良性貧血 / クロナリティ / 免疫抑制療法 / 細胞傷害性T細胞 / 片親性二倍体 / クローン性造血 / ゲノム変異 / 6pUPD / SLIT1 / CD109 / HLA-B*40:02 / HLA-Aアレル欠失血球 / エスケープ造血 / 可溶性HLAペプチドーム |
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| Outline of Final Research Achievements |
To determine genomic abnormalities responsible for clonal hematopoiesis in patients with aplastic anemia (AA), we analyzed peripheral blood DNA from 159 patients with aplastic anemia using a next generation sequencer. At least one gene abnormality was detectable in approximately 40% of the patient. Recurrent abnormalities included those of DNMT3 and ASXL1 that were often detected in patients with myelodysplastic syndrome (MDS). However, the presence of PIGA and BCOR/BCOR1 abnormalities were rather associated with good response to immunosuppressive therapy than the risk of evolving into MDS. In another attempt to clarify the immune mechanism of AA, we successfully isolated a cytotoxic T cell clone from an AA patient with uniparental disomy of chromosome 6p, which killed hematopoietic progenitor cells in a resitricted manner by HLA-DRB1*40:02.
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