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目的探索一种非受体型酪氨酸激酶2/信号转导子和转录活化子5(JAK2/STAT5)通路特异性抑制剂———苯亚甲基丙二腈脂类衍生物AG490对骨髓增生异常综合征-难治性贫血(MDS-RA)骨髓造血细胞细胞因子及信号转导的影响。方法建立MDS-RA骨髓造血细胞培养体系JAK2、STAT5、Bc l-xL基因表达的荧光定量聚合酶链反应(FQ-PCR)检测方法;粒单集落刺激因子(GM-CSF)激活10例MDS-RA骨髓单个核细胞培养液JAK2、STAT5、Bc l-xL表达,通过酶联免疫吸附试验(ELISA)方法检测AG490组、空白对照组培养体系上清细胞因子白细胞介素(IL)-2、IL-3、γ干扰素(IFN-γ)、肿瘤坏死因子(TNF-α)水平,FQ-PCR检测上述两组培养体系单个核细胞JAK2、STAT5、Bc l-xL基因表达拷贝数。结果AG490组IL-3、IFN-γ水平明显低于空白对照组(P<0.01),IL-2、INF-α水平差异无显著性;AG490组JAK2、STAT5、Bc l-xL基因表达与空白对照组比较,差异有显著性(P<0.05,P<0.01)。结论AG490可以调整MDS-RA骨髓造血细胞培养体系上清细胞因子水平,进而影响JAK2/STAT5通路信号转导,下调Bc l-xL表达。
Objective To explore the effect of AG490, a non-receptor tyrosine kinase 2 / signal transducer and activator of transcription 5 (JAK2 / STAT5) pathway specific inhibitor, on the bone marrow Effect of bone marrow hematopoietic cells on cytokines and signal transduction in patients with MDS-refractory anemia (MDS-RA). Methods The expression of JAK2, STAT5 and Bcl-xL in MDS-RA bone marrow-derived hematopoietic cell culture system was detected by fluorescence quantitative polymerase chain reaction (FQ-PCR). Granulocyte colony stimulating factor (GM-CSF) The expression of JAK2, STAT5 and Bc 1 -xL in RA bone marrow mononuclear cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA). The levels of interleukin (IL) -2, IL-2 The levels of JAK2, STAT5 and Bc1-xL gene expression in the two groups were detected by FQ-PCR. Results The levels of IL-3 and IFN-γ in AG490 group were significantly lower than those in blank control group (P <0.01), while the levels of IL-2 and INF-α in AG490 group were not significantly different. The expression of JAK2, STAT5 and Bcl- The difference between the two groups was significant (P <0.05, P <0.01). Conclusion AG490 can regulate the level of cytokines in MDS-RA bone marrow hematopoietic cell culture system, and then affect the signal transduction of JAK2 / STAT5 pathway and down-regulate the expression of Bcl-xL.