| Project/Area Number |
17K10130
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Gunma Institute of Public Health and Environmental Sciences |
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Principal Investigator |
Hayashi Yasuhide 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
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| Co-Investigator(Kenkyū-buntansha) |
大久保 淳 北海道大学, 大学病院, 医員 (30568754)
朴 明子 群馬県衛生環境研究所, 研究企画係, 研究員 (50450375)
外松 学 群馬県衛生環境研究所, 研究企画係, 研究員 (70251113)
山田 佳之 群馬県衛生環境研究所, 研究企画係, 研究員 (80309252)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 小児血液学 / 遺伝子 / マイクロアレイ / プロテオソーム / トランスクリプトーム / メチル化アレイ / RAS経路 / ITD |
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| Outline of Final Research Achievements |
We analyzed 330 clinical samples of pediatric AML patients in the JPLSG AML-05 trial. Targeted sequencing by next-generation sequencer was performed in these patients, using a 343-gene custom panel. MLPA method, SNP array and RNA-Seq were performed for 40-100 patients. Aberrations of RAS pathway genes, KMT2C, PHF6, MGA, TET2 genes, were identified. Association of the KIT-ITD and new several ITDs with clinical features was examined. We found 91 RAS pathway mutations as follows: PTPN11, 21; CBL, 8; NRAS, 49; KRAS, 13. NRAS mutations were frequently observed and were mutually exclusive with FLT3-ITD. Interestingly, all 3 patients with PTPN11 mutations lacking CBF-AML relapsed. Several genes were found to be associated with prognosis of pediatric AML, suggesting that pediatric AML will be stratified by these genetic results, and prognosis of the patients will be improved. Systemic methylation analysis will clarify a new mechanism of leukemogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
小児AMLのJPLSG AML-05登録症例に対し次世代シーケンサーを用いたRNA-Seq、全エクソン解析、343遺伝子カスタムパネルを用いたターゲットシーケンスを施行し、遺伝子異常と臨床像との関係を検討した。新規遺伝子や予後と相関する遺伝子を多数見出し、これらを用いて今後小児AMLを層別化して治療を行い、予後の改善に貢献するものと思われた。また成人との比較により、小児と成人のAMLの発生機序の相違や予後の相違について新たなメカニズムを見出し、発がん機序の解明に役立つと思われた。さらにメチル化解析を行っており、新たなメチル化の機序を見出し発癌と進展の解明に貢献すると思われた。
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