FBXW7在小鼠急性T淋巴细胞白血病模型中的表达

Expression of FBXW7 in a murine model of T-cell acute lymphoblastic leukemia

目的探讨抑癌基因FBXW7在Notch1诱导的小鼠白血病发展中的表达变化规律。方法采用Notch1过表达小鼠急性T淋巴细胞白血病移植模型，在发病不同阶段分离骨髓单个核细胞，并在发病晚期用流式细胞术分选CD45.2^GFP＋白血病细胞。实时定量PCR方法检测FBXW7的表达变化。结果对照组和白血病组小鼠骨髓细胞均表达FBXW7。Notchl过表达导致的小鼠白血病发展过程中，FBXW7在对照小鼠中表达水平逐渐升高；而在白血病小鼠中，随着白血病发展，表达水平逐渐下降，第12天降至对照组的1／60分选后的CD45.2＋GFP＋白血病细胞低表达FBXW7。结论FBXW7在小鼠白血病模型中低表达，提示FBXW7介导的泛素化降解途径异常可能与Notchl诱导小鼠白血病发生、发展相关。

Objective To investigate the expression of FBXW7 during the development of Notchl- induced murine leukemia. Methods Notchl over-expressing murine model of T-cell acute lymphoblastic leukemia was used to study the expression of FBXW7 by real-time PCR methods. Bone marrow mononuelear cells （BMNC） were isolated on different days after transplantation and CD4;2 GFP＋ leukemia cells were sorted by flow cytometry at late stage. The expression changes of FBXW7 were tested by real-time PCR. Results The mouse bone marrow cells both from leukemia and control groups expressed FBXW7. Different expression patterns of FBXW7 were observed during the development of leukemia. The expression of FBXW7 was gradually increased in control group, whereas the expression level of FBXW7 in leukemia group was decreased steadily and reached one-sixth of that in control group on 12th day. Furthermore, lower expression level of FBXW7 was observed in CD45.2＋ GFP＋ leukemia cells. Condusion Decreased expression of FBXW7 is observed in Notchl-induced mouse leukemia model, suggesting that the abnormal ubiquitin degradation pathway mediated by FBXW7 might contribute to the leukemogenesis in Notchl-indueed murine leukemia model.