Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish

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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: Tan, Jiaqi, Zhao, Lei, Wang, Gaoxiang, Li, Tongjuan, Li, Dan, Xu, Qian, Chen, Xing, Shang, Zhen, Wang, Jue, Zhou, Jianfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5998191/
https://www.ncbi.nlm.nih.gov/pubmed/30003105
http://dx.doi.org/10.1155/2018/6705842
Descripción
Sumario: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.

Ejemplares similares