Clarifying clonal architecture diversity of leukemia dervied from myelodysplastic syndromes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17412
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Nippon Medical School
• Principal Investigator: Nagata Yasunobu 日本医科大学, 医学部, 講師 (90739575)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 骨髄異形成症候群 / 次世代シーケンサー / クローン進化

Outline of Final Research Achievements

The purpose of this study was to analyze samples over time from myelodysplastic syndrome to acute leukemia in order to elucidate the mechanism of tumorigenesis that promotes tumorigenesis and ultimately progresses to leukemia.
Targeted sequencing analysis was used to identify gene mutations with high sensitivity, and the clonal evolution could be accurately tracked by focusing on allele frequencies. Correlation analysis with clinical information, including prognosis and adverse events, revealed that the response to novel drugs such as BCL2 inhibitors can be stratified by genetic abnormalities such as TP53 and IDH1/2.
These results are of great importance in predicting treatment response using genetic abnormalities and helping to select the optimal treatment for individual patients.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

遺伝子変異を持つ実際の患者に最も有効な治療法を選択する手法は定まっていないため、経時的試料を解析することで、腫瘍化を促進させ最終的に白血病に進展する腫瘍発症メカニズムを明らかにし、新たな治療戦略の構築に資することを目指していた。
本成果により、治療抵抗性に関わる遺伝子異常やその特徴が明らかとなり、実際の患者に適切な治療を選択するための新たな要因となった点で学術的意義が高い。
今後、前向きな臨床試験で本成果が検証され、治療成績の改善というエビデンスが期待される点で社会的意義が高いと考える。