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.
Keyphrases
- acute myeloid leukemia
- atrial fibrillation
- poor prognosis
- allogeneic hematopoietic stem cell transplantation
- endothelial cells
- genome wide
- genome wide identification
- copy number
- high throughput
- induced pluripotent stem cells
- long non coding rna
- pluripotent stem cells
- protein protein
- bone marrow
- emergency department
- drug delivery
- cell proliferation
- dna methylation
- immune response
- binding protein
- small molecule