Establishment of AML Mouse Model by Transplantation of Hematopoietic Cells from MLL-AF9 Transgenic Mice

Abstract

To establish a leukemia mouse model induced by transplantation of hematopoietic cells from mixed lineage leukemia (MLL)-AF9 transgenic mice so as to provide the basis for the mechanism research and drug screening of acute myeloid leukemia (AML). MLL-AF9 knock-in mice were bred and identified. When the mice developed leukemia, white blood cell (WBC) count in peripheral blood, flow cytometry and morphology method were analyzed to identify the disease. When the WBC count in peripheral blood was more than 100×109/L, bone marrow cells and spleen cells were collected and cryopresevated. After resuscitation, the cells were injected into 4.5 Gy irradiated wild C57BL/6J mice through the tail vein to develop MLL-AF9 leukemia mouse model. Finally, the therapeutic effect was evaluated by positive drug on the model. The natural onset times of leukemia on MLL-AF9 knock-in mice were 22-28 weeks. The spleens of the transgenic mice enlarged and the bone marrow showed the immature forms of myeloid leukemia cells. Both the bone marrow and spleen cells highly expressed myeloid markers, CD11b and Gr-1. At least 0.5×106 bone marrow cells and 2.5×106 spleen cells could induce leukemia in all recipient mice, and the median survival times of mice were 20 days and 36 days, respectively. Experimental treatment was carried out on the leukemia mouse model transplanted with MLL-AF9 spleen cells, and it was found that the traditional chemotherapy drug cytarabine could delay the onset of leukemia and prolong the survival time of the mouse model. The leukemia model of hematopoietic cell transplantation based on MLL-AF9 transgenic mice is successfully established, which can be used for the study of the pathogenesis and evaluation of therapeutic effect of AML.