2019 Fiscal Year Final Research Report
The molecular pathogenenesis of pediatric acute lymphoblastic leukemia through the understanding of clonal artitectures
| Project/Area Number |
17K10136
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | National Hospital Organization Nagoya Medical Center |
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Principal Investigator |
Masashi Sanada 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 高度診断研究部長 (20529044)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 急性リンパ性白血病 / クローン |
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| Outline of Final Research Achievements |
For the purpose of identifying of Ig/TCR rearrangements in acute lymphoblastic leukemia (ALL), a comprehensive analysis of rearrangements using target-capture sequencing was performed, and in addition to the rearrangements used for the measurement of minimal residual disease, an extremely large number of rearrangements were detected. A time-course study of relapsed B-ALL cases suggests that the time to relapse, clonal diversity at the time of initial diagnosis, and depth of remission contributed to clonal changes. Understanding the clonal structure was considered important for understanding the pathogenesis of ALL and monitoring after treatment.
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| Free Research Field |
分子遺伝学、造血器腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
ALL診療において、腫瘍細胞特異的なIg/TCR再構成に基づく、微小残存病変の定量評価は、治療反応性を直接的に反映し、治療最適化に必須の検査となっている。PCR-MRDにおいて、腫瘍細胞特異的な再構成の同定の過程は非常に煩雑であったが、今回開発した検出系は効率的であり、有用性が高い。クローン構造の理解は、白血病の病態理解ならびに治療後のモニタリングのみならず、ALL以外のリンパ系腫瘍用においても有用であり、形質細胞性腫瘍のゲノム解析にも応用可能であった。
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