动物造模,药效评价,白血病 z-bio 2024-06-19 368

　　【 Modeling Mechanism 】 Chronic myeloid leukemia (CML) is a type of malignant tumor that involves bone marrow hematopoietic stem cells. Ph chromosome or bcr/Abl positivity is a molecular genetic characteristic of CML patients. Therefore, using a reverse transcription virus vector expressing the bcr/Abl fusion gene to transfect mouse bone marrow cells and transplant normal mice can prepare an animal model of chronic myeloid leukemia based on this gene.

　　【 Modeling Method 】 Bone marrow cells of female BALB/c mice were isolated and transfected with a retroviral vector expressing the bcr/Abl fusion gene. After screening, 1 × 100000 to 2 × 100000 were injected into homologous male BALB/c mice irradiated with a lethal dose (900cGy) for 6-12 weeks. The mice exhibited CML related symptoms and acute lymphocytic leukemia.

　　【 Model features 】 When V-Abl or bcr/Abl retroviral vectors were transfected into mouse hematopoietic stem cells, 90% of mice developed tumors regardless of the form of the Abl gene. By using MCS retroviral vector and increasing the viral titer of the bcr/Abl fusion gene, the incubation period of CML was significantly shortened. All mice receiving transfected cells developed CML after a 4-6 week incubation period. The main changes include a significant increase in peripheral blood white blood cells, splenomegaly, and high expression of BCR/ABL fusion proteins.

　　【 Model Evaluation and Application 】 Approximately 50% of CML animal models prepared by V-Abl or bcr/Abl retroviral vector transfection exhibited abnormal bone marrow proliferation, which shares many similarities with the characteristics of human chronic myeloid leukemia in the chronic phase, while the remaining mice exhibited abnormal proliferation of B lymphocytes. Animal models of CML prepared by using MCS retroviral vectors and increasing the viral titer of bcr/Abl fusion genes often die rapidly in the short term, without experiencing a chronic phase similar to human CML, and with significant pulmonary bleeding, which is rare in human CML.