Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish
Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish
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人类 MLL-AF9 过度表达诱导斑马鱼异常造血扩张
DOI：
10.1155/2018/6705842
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Zhou，Jianfeng
中科院分区：
文献类型：
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作者：
Tan，Jiaqi;Zhao，Lei;Zhou，Jianfeng
混合系白血病1（MLL 1）基因的11 q23在早期胚胎发育和造血中起着至关重要的作用。MLL-AF 9融合基因是由染色体易位引起的，常导致预后不良的急性髓系白血病。在这里，我们产生了表达人MLL-AF 9融合基因的斑马鱼模型。显微注射人MLL-AF 9 mRNA到斑马鱼胚胎中导致造血增强和下游基因如meis 1和hox簇基因的激活。胚胎MLL-AF 9表达上调HSPC和髓系标志物。多柔比星和MI-2（一种脑膜炎蛋白抑制剂）治疗显著恢复了MLL-AF 9表达动物的正常造血。本研究为深入了解MLL-AF 9在斑马鱼造血中的作用提供了新的思路，并为高通量药物筛选建立了一个稳健有效的体内模型。
The 11q23 of the mixed lineage leukemia 1 (MLL1) gene plays a crucial role in early embryonic development and hematopoiesis. The MLL-AF9 fusion gene, resulting from chromosomal translocation, often leads to acute myeloid leukemia with poor prognosis. Here, we generated a zebrafish model expressing the human MLL-AF9 fusion gene. Microinjection of human MLL-AF9 mRNA into zebrafish embryos resulted in enhanced hematopoiesis and the activation of downstream genes such as meis1 and hox cluster genes. Embryonic MLL-AF9 expression upregulated HSPC and myeloid lineage markers. Doxorubicin and MI-2 (a menin inhibitor) treatments significantly restored normal hematopoiesis in MLL-AF9-expressing animals. This study provides insight into the role of MLL-AF9 in zebrafish hematopoiesis and establishes a robust and efficient in vivo model for high-throughput drug screening.