Objective: To explore whether BAX plays a role in the development of Philadelphia chromosome-positive leukemia and related mechanisms.
Methods: Target-gene knockout mice were used as bone marrow cell donors. Retrovirus over-expressing BCR-ABL were packaged. BCR-ABL-induced B-ALL mouse model was established through donor's B cells transfected by the retrovirus and the B cells over-expressing BCR-ABL were given to the receptor mice by tail vein injection. Western blot was used to detect the protein express and flow cytometry was used to analyze the B cell subpopulations in BAX-/- and WT mouse bone marrows. Kaplan-Meier analysis was used to estimate the survival of diseased mice.
Results: BAX deletion caused faster development of BCR-ABL-induced leukemia in vitro and in vivo. BCR-ABL increased BCL-2 expression and enhanced BCL-2/BAX heterodimer formation.
Conclusion: The BAX deletion can accelerate the disease progression of BCR-ABL induced B-ALL.
题目: BAX基因缺失加速BCR-ABL诱导的小鼠B-ALL疾病进程.
目的: 探讨BAX对BCR-ABL诱导的小鼠B-ALL的发生、发展的影响及相关机制.
方法: 以目的基因敲除小鼠作为骨髓细胞供体；包装过表达BCR-ABL的逆转录病毒；通过逆转录病毒感染供体B-细胞和将过表达BCR-ABL的B-细胞尾静脉注射给受体小鼠，构建BCR-ABL诱导的B-ALL小鼠模型。采用Western blot检测蛋白的表达，采用流式细胞术分析细胞，用Kaplan-Meier曲线分析发病小鼠生存期.
结果: BCR-ABL转染的BAX缺失B-细胞比野生型B-细胞在体外和受体小鼠体内增长更快；BAX缺失供体B-细胞构建的疾病小鼠的生存期更短。BCR-ABL增加BCL-2表达和BCL-2/BAX异二聚体形成.
结论: BAX缺失会加速BCR-ABL诱导的小鼠B-ALL疾病进程.