Construction of Mouse Acute Myeloid Leukemia Model
Hui Xinhui1,2, Wan Xiaoling2, Yu Fangfang3, He Qiaomei3, Zhang Yan2*, Zhang Wenju1*
Abnormal rearrangements of MLL gene cause acute lymphoid (ALL) and acute myeloid leukemia (AML). Here, we describe a method of construction of a mouse AML model using a MLL-AF9 retroviral system. We compared the efficiencies of Lineage–(Lin–) bone marrow cells enrichent by using immunomagnetic beads and 5-fluorouracil (5-FU) treatment, and efficiencies of two different infection strategies. We found that 5-FU treatment of mice and 2-round of infection of Lin– bone marrow cells with viral supernatant 48 h post-transfection would lead to a highly efficient infection of MLL-AF9 retroviral vector. Moreover, sixty days after transplantation of MLL-AF9-infected Lin- bone marrow cells, leukemia cells were observed in the peripheral blood, and infiltration of leukemia cells were detected in the bone marrow and spleen of the recipients. In addition, RT-qPCR results verified a significant increase of transcription of MLL-AF9-targeted genes, further indicating an establishment of the AML mouse model. Our study provides a useful tool of studying the molecular mechanisms of leukemia pathogenesis and development of novel therapies.
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