Comprehensive genetic analysis in pediatric acute myeloid leukemia to elucidate the clinical significance of genes on chromosome 7.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20937
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• 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: Kaburagi Taeko 群馬県衛生環境研究所, 研究企画係, 研究員 (20907084)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 小児 / 急性骨髄性白血病 / パネルシーケンス / 7番染色体 / KMT2C

Outline of Final Research Achievements

Identification of novel prognostic factors is urgently needed to improve the prognosis of pediatric acute myeloid leukemia (AML). We focused on monosomy 7 and deletion of the long arm of chromosome 7[del(7q)], which are representative chromosomal abnormalities in AML, and performed mutation analysis and copy number analysis of genes on chromosome 7 using next-generation sequencing to verify their clinical significance. Monosomy 7 was significantly associated with poor prognosis, while del(7q) was not associated with prognosis. MECOM high expression was significantly more common in monosomy 7 but not in del(7q), suggesting that monosomy 7 and del(7q) have different molecular biological backgrounds. As for genetic mutations on the long arm of chromosome 7, patients with KMT2C mutations had a significantly poorer prognosis, suggesting that KMT2C mutations may be an important prognostic factor in pediatric AML.

Free Research Field

小児急性骨髄性白血病

Academic Significance and Societal Importance of the Research Achievements

小児急性骨髄性白血病(AML)において、これまでもmonosomy 7と7番染色体長腕欠損[del(7q)]は着目され、それらの共通欠失領域に重要な遺伝子が存在することが考えられてきたが、いまだに責任遺伝子の同定には至っていない。本研究ではmonosomy 7と7番染色体長腕欠損[del(7q)]の予後が異なり、背景としてmonosomy 7にはMECOM高発現の合併が多い一方、del(7q)には少ないなど、分子生物学的背景が大きく異なることが考えられた。これらは7番染色体上にはMonosomy 7やdel(7q)の共通欠失領域以外に重要な因子がある可能性を示唆する新たな知見と考えられた。