| Project/Area Number |
17K16186
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | フィラデルフィア染色体陽性急性リンパ性白血病 / BCR切断点 / BCR-ABL融合遺伝子 / 血球系統 / BCR遺伝子切断点 / 好中球FISH / 組織FISH / 内科 / 血液内科学 / 血液腫瘍学 |
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| Outline of Final Research Achievements |
Multi-lineage BCR-ABL expression (Multi-Ph) was defined in 21 of 59 patients (36%). BCR breakpoint was major in 17 of 21 Multi-Ph (81%). In such patients, BCR-ABL was detected at the multipotent progenitor level. However, no IKZF1 deletion patterns that were specific for Multi-Ph were identified. On the other hand, better survival rates were observed in patients with Multi-Ph compared with survival rates in those with uni-lineage BCR-ABL expression. In multivariate analyses, Multi-Ph was identified as a good prognostic factor for both overall survival and event-free survival. We confirmed Multi-Ph in more than one-third of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Although no specific molecular characteristics were identified, Multi-Ph was associated with better treatment outcomes.
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| Academic Significance and Societal Importance of the Research Achievements |
フィラデルフィア染色体陽性急性リンパ性白血病(Ph+ALL)においてBCR-ABL融合遺伝子が白血病芽球以外に発現している例が3分の１以上と一定の割合であることを示した。さらに、発現系統の違いが治療成績とも関連があり、BCR-ABL融合遺伝子が白血病芽球以外に発現していることが予後良好と関連することを示した。このことは、Ph+ALLにおける新たな予後因子としてBCR-ABL融合遺伝子の発現血球系統の違いが有用であることを示唆している。さらに背景にあると思われる遺伝子異常等の違いを明らかにすることでPh＋ALLの層別化につながると考えられる。
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