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Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish.


ABSTRACT: 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.

SUBMITTER: Tan J 

PROVIDER: S-EPMC5998191 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish.

Tan Jiaqi J   Zhao Lei L   Wang Gaoxiang G   Li Tongjuan T   Li Dan D   Xu Qian Q   Chen Xing X   Shang Zhen Z   Wang Jue J   Zhou Jianfeng J  

BioMed research international 20180530


The 11q23 of the mixed lineage leukemia 1 (<i>MLL1</i>) gene plays a crucial role in early embryonic development and hematopoiesis. The <i>MLL-AF9</i> fusion gene, resulting from chromosomal translocation, often leads to acute myeloid leukemia with poor prognosis. Here, we generated a zebrafish model expressing the human <i>MLL-AF9</i> fusion gene. Microinjection of human <i>MLL-AF9</i> mRNA into zebrafish embryos resulted in enhanced hematopoiesis and the activation of downstream genes such as  ...[more]

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