Refinement of the risk-stratified therapy for pediatric acute myeloid leukemia based on genetic abnormalities and onset age

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17322
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Gunma University
• Principal Investigator: Hara Yusuke 群馬大学, 医学部附属病院, 助教 (20806434)
• Project Period (FY): 2022-12-19 – 2024-03-31
• Keywords: 小児がん / 急性骨髄性白血病

Outline of Final Research Achievements

This study allowed us to analyze the characteristics of molecular abnormalities in pediatric acute myeloid leukemia based on onset age. It was found that there was a large bias in the frequency of molecular abnormalities between infants and older children, and that prognostic predictions differed significantly by age, even in cases with the same genetic abnormality. The results indicate that treatment and analysis of infants and older children as a distinct population may allow us to make more precise risk-stratified therapy. TP53 was detected in a subset of the older children, and these patients were expected to have a similar pathogenesis to that of adults with AML; those with TP53 had a very poor prognostic outcome and should be considered for inclusion in risk stratification as a poor prognostic factor.

Free Research Field

小児がん

Academic Significance and Societal Importance of the Research Achievements

小児急性骨髄性白血病(AML)は稀な小児がんであり、長期生存率は60-70%程度のいまだ予後不良の疾患である。成人の白血病とは異なる発症機序を持ち、また治療法も成人とは異なるため、小児に特化した治療が必要になる。そのためには小児例の詳細な研究が必要であるが、世界的に見ても小児AMLの研究の進展は十分ではない。本研究では小児AMLの遺伝子解析を網羅的に行い、特に年齢に着目することで、小児AMLと一括りにされている疾患を更に乳幼児と年長児に分けて解析することができた。乳幼児と年長児のAMLは細かい点で異なることも多く、今回得た知見を治療に応用することで更に治療成績が向上することが期待される。