Analysis of molecular abnormalities and development of risk-stratified therapy in infants with acute myeloid leukemia
| Project/Area Number |
17H06554
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Gunma University |
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Principal Investigator |
Hara Yusuke 群馬大学, 医学部附属病院, 助教 (20806434)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 小児急性骨髄性白血病 / 遺伝子解析 / リスク層別化治療 / 乳幼児における急性骨髄性白血病 / 乳幼児に特化した層別化治療 / 予後因子の探索 / 癌 / 遺伝子 / 白血病 |
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| Outline of Final Research Achievements |
In this study, we aimed to identify genetic abnormalities specific to infant acute myeloid leukemia (AML), and to make more appropriate risk-stratified therapy for this disease. We analyzed clinical samples obtained from the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 trial. We found CBFA2T3-GLIS2 and NUP98-KDM5A fusion genes as poor prognostic markers. Whereas, the prognosis of KMT2A-rearrangement and CBFB-MYH11 fusion genes, which are found in all age-groups of pediatric AML, were different between infants and older pediatric patients. Moreover, we performed next generation sequencing using clinical samples of patients lacking well-known genetic prognostic markers, and identified various novel genetic abnormalities. These findings will contribute to make the refined risk-stratified therapy for infant AML.
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| Academic Significance and Societal Importance of the Research Achievements |
小児の急性骨髄性白血病(AML)の治療成績は60%程度であり、治療成績の改善が望まれている。また、小児AMLの中でも各年齢でその特徴や治療成績は異なり、各年齢層の特徴に応じた治療の強化や減弱を行うことで、より治療成績は改善すると予測される。本研究では特に乳幼児例に主眼を置いて詳細な遺伝子解析及び臨床的意義の解析を行った。一部の遺伝子異常は乳幼児と年長児で異なる予後を辿ることが判明し、年齢を考慮せずに小児AMLを画一的に治療することは、症例によっては治療強度を誤ってしまう可能性が示された。また、新規の遺伝子異常を多数発見したため、治療に応用できるよう今後より詳細な解析を行う予定である。
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Report
(3 results)
Research Products
(3 results)
