Establishment of Mouse Model with Humanized Chronic Myeloid Leukemia

Abstract

To establish a BALB/c nude mouse model with the huamanized chronic myeloid leukemia (CML) for the study of human CML. The BALB/c nude mice aged 4 weeks pretreated by splenectomy, the cyclophosphamide intraperitoneal injection and sublethal irradiation (SLI) were transplanted intravenously with bone marrow mononuclear cells from CML patients. The SLI-pretreated nude mice were divided into 2 groups: group A, in which the nude mice were injected with 0.3 ml PBS; group B, in which the nude mice were infused intravenously with 4.5×107 mononuclear cells from CML patients. Then the changes of body weight and appetite were observed, the hemogram and cell morphology were determined, the expressions of human CD13 and CD45 were detected by flow cytometry, the pathologic analysis of bone, liver and intestine were performed by biopsy, and the BCR/ABL fusion gene was detected by RT-PCR. The mice in group B displayed weakness, auantic, less foodintake and instabiligy of gait as time want on. The average survival time was 46.2±4.2 d (45-57 d). On the third week, the CD13+CD45+ cells accounted for 0.56±0.05% and 2.56±0.36% respectively in group A and B. While on the sixth week, the CD13+CD45+ cells accounted for 0.44±0.07% and 4.97±0.43% in A and B groups respectively, these results showed that cell count in B group was significantly higher than that in A group(P<0.05). Pathological examination showed that the leukemic cells were found in bone marrow of group B. The BCR/ABL fusion gene could be detected in bone marrow. BALB/c nude mouse model with huamanized chronic myeloid leukemia(CML) model has been established by pretreating mice with SLI. The survival time of mice in this model has been long, and the cost to establish the model is low.