Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish

Abstract EN

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.