2021 Fiscal Year Final Research Report

Process of in utero leukemogenic fusion gene generation in childhood acute leukemia

Research Project

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Project/Area Number	19K08866
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54010:Hematology and medical oncology-related
Research Institution	Ehime University
Principal Investigator	EGUCHI MARIKO 愛媛大学, 医学系研究科, 教授 (40420781)
Co-Investigator(Kenkyū-buntansha)	江口峰斉愛媛大学, 医学部附属病院, 准教授 (50420782)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	白血病 / MLL融合遺伝子 / 遺伝的背景 / iPS細胞
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.
Free Research Field	小児血液腫瘍学
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。