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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.

Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish