Human MLL-AF9 Overexpression Induces Aberrant Hematopoietic Expansion in Zebrafish.

BioMed Research International
Jiaqi TanJianfeng Zhou

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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Citations

Sep 15, 2019·Disease Models & Mechanisms·Martina KonantzClaudia Lengerke
Dec 3, 2020·Current Opinion in Hematology·Samuel J Wattrus, Leonard I Zon
Dec 6, 2020·Current Opinion in Hematology·Samuel J Wattrus, Leonard I Zon
May 16, 2021·The Science of the Total Environment·Xin Chen, Wenhua Li

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Methods Mentioned

BETA
in
PCR
Reverse Transcription PCR
transgenic

Software Mentioned

GraphPad Prism

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