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ZIRC
ZFIN ID: ZDB-PUB-180714-6
Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish
Tan, J., Zhao, L., Wang, G., Li, T., Li, D., Xu, Q., Chen, X., Shang, Z., Wang, J., Zhou, J.
Date: 2018
Source: BioMed Research International   2018: 6705842 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Animals
  • Disease Models, Animal
  • Hematopoiesis/genetics*
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Leukemia, Myeloid, Acute/genetics*
  • Myeloid-Lymphoid Leukemia Protein/physiology*
  • Oncogene Proteins, Fusion/physiology*
  • Translocation, Genetic*
  • Zebrafish
PubMed: 30003105 Full text @ Biomed Res. Int.
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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.
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