Process of in utero leukemogenic fusion gene generation in childhood acute leukemia
| Project/Area Number |
19K08866
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Ehime University |
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Principal Investigator |
EGUCHI MARIKO 愛媛大学, 医学系研究科, 教授 (40420781)
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| Co-Investigator(Kenkyū-buntansha) |
江口 峰斉 愛媛大学, 医学部附属病院, 准教授 (50420782)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 白血病 / MLL融合遺伝子 / 遺伝的背景 / iPS細胞 / 白血病幹細胞 / 小児 / 遺伝子異常 |
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| Outline of Research at the Start |
急性白血病は小児期で最も多いがんである。抗がん剤の多剤併用による化学療法の発展により、その治療成績は改善したが、化学療法によって障害を残し、治癒後長期にわたり後遺障害に苦しむ患者も少なくない。近年分子標的療法として、白血病特異的な遺伝子異常をターゲットとした治療法が開発・応用されているが、白血病の後遺症なき根治のための戦略として有効な方法は分子標的療法に加えて、その発症予防および再発予防である。本研究では、小児急性白血病の発症に至るプロセス、特に白血病幹細胞の成立に必須な遺伝子異常の獲得プロセスを解明し、小児急性白血病の発症および再発予防の可能性について検討することを目的とする。
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| Outline of Final Research Achievements |
To clarify the process leading to generation of MLL fusion gene in utero, hematopoietic cell differentiation using patient-derived iPS cells were analyzed. iPS cells were established from the peripheral blood of three patients with MLL fusion gene-positive leukemia in remission as well as from three healthy adults. Established iPS cells were differentiated into CD34-positive hematopoietic progenitor cells and further differentiated into B lymphocyte progenitor cells. During the process of hematopoietic differentiation, generation of MLL fusion gene was examined by the inverse PCR method. Hematopoietic progenitor cells obtained from all three patient-derived iPS cells harbored MLL fusion gene in low frequency, which was not detected in iPS from healthy controls. Formation of MLL fusion gene did not depend on the addition of TopoII inhibitor. It was suggested that some, yet unknown genetic background of the patient may be involved in the generation of the MLL fusion gene.
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| Academic Significance and Societal Importance of the Research Achievements |
MLL融合遺伝子を有する乳児急性リンパ性白血病は、予後の改善が著しい小児白血病の中で、今なお治療抵抗性の白血病である。MLL融合遺伝子陽性乳児白血病の発症過程を明らかにし、発症予防につながる情報を得るため、患者細胞より樹立したiPS細胞を用いた造血細胞への分化系を確立し、白血病発症の初期段階のMLL融合遺伝子の形成のメカニズムについて検討した。その結果MLL融合遺伝子の形成には患者が有する何らかの要因（遺伝的背景など）が関与している可能性が示唆された。この遺伝的背景と、関与しうる環境要因などの外的因子を明らかにすることにより、MLL融合遺伝子陽性の乳児白血病の発症予防につながる可能性がある。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Renal dysfunction can occur in advanced-stage Duchenne muscular dystrophy.2020
Author(s)
Motoki T, Shimizu-Motohashi Y, Saito I, Komaki H, Ishiyama A, Aibara K, Jogamoto T, Tezuka Y, Kawabe M, Makino A, Nagatani K, Tatara K, Kuwabara K, Kikuchi C, Fukuda M, Ishii E, Eguchi M
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Journal Title
Muscle and Nerve
Volume: 61
Issue: 2
Pages: 192-197
DOI
Related Report
Peer Reviewed
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[Journal Article] Nonocclusive Mesenteric Ischemia Rescued by Immediate Surgical Exploration in a Boy with Severe Neurodevelopmental Disability.2019
Author(s)
Mizumoto M, Ochi F, Jogamoto T, Okamoto K, Fukuda M, Yamauchi T, Miyata T, Tashiro R, Eguchi M, Kitazawa R, Ishii E
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Journal Title
Case Reports in Pediatrics
Volume: 2019
Pages: 1-4
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Early detection of the PAX3-FOXO1 fusion gene in circulating tumor-derived DNA in a case of alveolar rhabdomyosarcoma2019
Author(s)
Eguchi-Ishimae M, Tezuka M, Kokeguchi T, Nagai K, Moritani K, Yonezawa S, Tauchi H, Tokuda K, Ishida Y, Ishii E, Eguchi M
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Journal Title
Genes Chromosomes Cancer
Volume: 印刷中
Issue: 8
Pages: 521-529
DOI
Related Report
Peer Reviewed / Open Access
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