PUBLICATION

Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish

Authors
Tan, J., Zhao, L., Wang, G., Li, T., Li, D., Xu, Q., Chen, X., Shang, Z., Wang, J., Zhou, J.
ID
ZDB-PUB-180714-6
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.
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.
Errata / Notes
This article is corrected by ZDB-PUB-220202-35
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping