Developmental impact of MLL-AF4fusion gene on early hematopoieticstem cells

MLL-AF4融合基因对早期造血干细胞发育的影响

• 批准号: 22591162
• 负责人: EGUCHI Mariko
• 金额: $ 2.91万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591162/
• 关键词: 小児腫瘍学; MLL; ES細胞; 造血細胞分化; 白血病

To study the developmental impact of MLL-AF4 fusion gene on early hematopoietic development, mouse embryonic stem (ES) cells with constitutive expression of MLL-AF4 were established. When hematopoietic differentiation was examined by embryoid body (EB) formation, Tie2^+c-kit^+cells which contain early hematopoietic stem cells were significantly reduced in MLL-AF4 expressing Ebs compared to that of control Ebs.Expression array analysis indicated that MLL-AF4 works as positive regulator of gene expression up-regulating various genes. Several genes up-regulated by MLL-AF4 were known to have important roles in cell differentiation to mesenchymal lineage, whereas transcriptional regulator of hematopoietic lineage were down-regulated. These MLL-AF4 expressing pre-hematopoietic stem cells with mesenchymal nature, were unable to cause leukemia in vitroor in vivo, showing that some secondary event is necessary to cause leukemia. MLL-AF4, having the potential to influence early hematopoietic cell differentiation, may cause leukemic transformation whenaccompanied by some important additional genetic events.

为了研究MLL-AF4融合基因对早期造血发育的影响，我们构建了MLL-AF4组成表达的小鼠胚胎干细胞（ES）。当通过胚状体（EB）形成检测造血分化时，与对照Ebs相比，含有早期造血干细胞的Tie2^+c-kit^+细胞在表达MLL-AF4的Ebs中显著减少。表达阵列分析表明MLL-AF4作为基因表达的正调控因子上调了多种基因的表达。已知MLL-AF4上调的几个基因在细胞向间充质谱系分化的过程中起重要作用，而造血谱系的转录调节因子则下调。这些表达MLL-AF4的造血前干细胞具有间充质性质，在体外不能引起白血病，表明一些继发性事件是引起白血病的必要条件。MLL-AF4具有影响早期造血细胞分化的潜力，当伴随着一些重要的额外遗传事件时，可能导致白血病转化。

项目成果

小児白血病とTEL遺伝子異常

儿童白血病和 TEL 基因异常

• 发表时间: 2011
• 期刊: 臨床血液
• 作者: 江口真理子;石前峰斉
• 通讯作者: 石前峰斉

ETV6-ARNT fusion in a patient with childhood T lymphoblastic leukemia

• DOI: 10.1016/j.cancergencyto.2010.07.121
• 发表时间: 2010-10-01
• 期刊: CANCER GENETICS AND CYTOGENETICS
• 作者: Otsubo, Keisuke;Kanegane, Hirokazu;Miyawaki, Toshio
• 通讯作者: Miyawaki, Toshio

Clinical features and outcome of X-linked lymphoproliferative syndrome type 1 (SAP deficiency) in Japan identified by the combination of flow cytometric assay and genetic analysis

• DOI: 10.1111/j.1399-3038.2012.01282.x
• 发表时间: 2012-08-01
• 期刊: PEDIATRIC ALLERGY AND IMMUNOLOGY
• 影响因子: 4.4
• 作者: Kanegane, Hirokazu;Yang, Xi;Miyawaki, Toshio
• 通讯作者: Miyawaki, Toshio

リンパ球機能異常と類縁疾患 原発性免疫不全症候群Ataxia-telangiectasia、日本臨床別冊 血液症候群(第2版)II -その他の血液疾患を含めて

淋巴细胞功能异常及相关疾病原发性免疫缺陷综合症共济失调毛细血管扩张症，日本临床特别版血液综合症（第二版）II - 包括其他血液疾病

• 发表时间: 2013
• 作者: 石前峰斉;江口真理子
• 通讯作者: 江口真理子

Concordant expression of TEL-AML1 fusion and c-Myc amplification in a patient with B-precursor ALL

B 前体 ALL 患者中 TEL-AML1 融合和 c-Myc 扩增的一致表达

• 发表时间: 2010
• 作者: 岡田 賢,小林正夫,Luyan Liu;Xiao-Fei Kong;Alexandra Y. Kreins;Sophie Cypowyj;Laurent Abel;Capucine Picard;Stephanie Boisson-Dupuis;Anne Puel;Jean-Laurent Casanova;橋井佳子;河上早苗
• 通讯作者: 河上早苗