2018 Fiscal Year Final Research Report
Comprehensive gene analysis of clonal hematopoiesis in childhood aplastic anemia
Project/Area Number |
17K16248
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Nagoya University |
Principal Investigator |
Atsushi Narita 名古屋大学, 医学部附属病院, 助教 (20625149)
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Research Collaborator |
TAKAHASHI Yoshiyuki
MURAMATSU Hideki
OKUNO Yusuke
NAKATOCHI Masahiro
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Project Period (FY) |
2017-04-01 – 2019-03-31
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Keywords | 再生不良性貧血 / 発作性夜間血色素尿症 |
Outline of Final Research Achievements |
We retrospectively studied 57 children with Aplastic anemia (AA) between 1992 and 2010. During the follow‐up, five patients developed clinical PNH, in whom somatic PIGA mutations were detected by targeted sequencing. The 10‐year probability of clinical PNH development was 10.2% (95% CI, 3.6%-20.7%). Furthermore, the detection of minor PNH clones by flow cytometry at AA diagnosis was a risk factor for the subsequent development of clinical PNH. We performed whole-exome sequencing (WES) of paired bone marrow-germline reference samples in 41 patients. WES detected reccurent gene X mutations as a novel mutational target. Gene X mutation may be associated the pahophisiology of AA.
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Free Research Field |
小児血液腫瘍学
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Academic Significance and Societal Importance of the Research Achievements |
小児再生不良性貧血(AA)に発作性夜間血色素尿症(PNH)が合併することが知られている。我々は小児AA患者57例をの長期予後を調査したところ、観察期間中に5例がPNHを発症しており、10年累積発症率は10.2% (95% CI, 3.6%-20.7%)であった。また、AAからPNHを発症した5例では、AA診断時のフローサイトメトリーで微小PNH血球が全例で陽性であった。AA診断時とPNH発症時の検体をターゲットシーケンス解析した結果、AA診断時にはPIGA遺伝子変異を認めなかったが、PNH発症後にPIGA遺伝子変異を全例で検出した。
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