Establishment of a human chronic myeloid leukemia-like mouse model

AIM：To establish a new model of chronic myeloid leukemia (CML) for further studying the pathogenesis mechanisms and discovering new therapeutic targets of this disease. METHODS：The retroviral packaging technique was improved by increasing retroviral titer with higher-quality plasmid, better cell state and appropriate cell seeding density for further studying. Donor BALB/c mice were pretreated with 5-fluorouracil (5-FU), and their bone marrow cells were infected with p210 BCR/ABL retroviral supernatant (BCR/ABL group) or empty retroviral vector (MigR1) supernatant (MigR1 group). Infected bone marrow cells were transplanted into lethally irradiated recipient BALB/c mice via tail vein. The activities of the mice were observed after bone marrow transplantation (BMT). The morphology of peripheral blood cells and bone marrow cells, and the pathological changes of the liver and spleen in dying mice were also determined. RESULTS：Retroviral packaging efficiency was improved by optimizing the experimental conditions with higher-quality plasmid, better cell state and appropriate cell seeding density. All mice in BCR/ABL group died at 19 to 25 d after BMT. Their myelocytes, metamyelocytes and mature granulocytes in peripheral blood and bone marrow were abundant. Hepatosplenomegaly and granulocyte infiltration in the liver and spleen were also observed. All mice in MigR1 group were normal. CONCLUSION: We have successfully set up a mouse model of CML by increasing retroviral titer with improved retroviral packaging technique, transfecting BCR/ABL into mouse bone marrow cells in vitro and transplanting the cells to the recipients of the same lineage.