Comprehensive analysis of gene mutations for precision medicine in pediatric acute myeloid leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 19K21333
• Project/Area Number (Other): 18H06234 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0904:Internal medicine of the bio-information integration and related fields
• Research Institution: Gunma Institute of Public Health and Environmental Sciences
• Principal Investigator: Genki Yamato 群馬県衛生環境研究所, 研究企画係, 研究員 (90825720)
• Project Period (FY): 2018-08-24 – 2020-03-31
• Keywords: 急性骨髄性白血病 / 小児 / 遺伝子異常

Outline of Final Research Achievements

Currently, the long-term survival rate of pediatric acute myeloid leukemia (AML) improved 60-70%. Recently, clinical sequences are used to determine the therapeutic methods of many cancers. Pediatric AML is also needed more genome information to perform clinical sequences for precision medicine. Here, we performed targeted sequencing using a 343-gene custom panel and next-generation sequencer in pediatric patients with de novo AML. As a result, we found recurrent gene mutations such as PTPN11, TET2, and TP53 which might be associated with outcome of AML. And we reported these results in the 60th and 61st American Society of Hematology Annual Meeting. Now, we have performed further analyses to determine the relations between genetic mutations and clinical features and prepared for submitting these significant results.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

近年がん領域で米国を中心にクリニカルシーケンスが実臨床に用いられるようになり、国内においても普及し始めている。クリニカルシーケンスは解析で得られた網羅的な患者ゲノム情報を基に治療方針や治療薬の選択が行われ、プレシジョンメディスンとほぼ同義である。治療方針の決定は過去の学術論文や構築されたデータベースを基盤としている。小児急性骨髄性白血病(AML)においても予後因子となりうる遺伝子変異の同定は急務である。本研究は小児AMLの網羅的遺伝子解析を行い、予後に関与しうる複数の遺伝子を同定した今後のプレシジョンメディスンへの基礎となりうる研究であり、将来の小児AML予後改善へつながる可能性を持っている。