MDS-RA骨髓造血细胞JAK2/STAT5通路活化及AG490干预研究  

Effect of AG490 on JAK2/STAT5 signal transduction pathway in bone marrow hematopoietic cells of MDS-RA

作　　者：田胜利[1] 周永明[2] 葛垒[3] 周韶红[2] 何玮[4] 薛志忠[4] 胡明辉[2] 许毅[2] 罗梅宏[2] 

机构地区：[1]上海中医药大学附属龙华医院,上海200032 [2]上海岳阳中西医结合医院血液科,上海200437 [3]中山医科大学达安基因诊断中心,广东广州510080 [4]上海岳阳中西医结合医院检验科,上海200437

出　　处：《检验医学》2006年第3期278-280,共3页Laboratory Medicine

摘　　要：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 investigate the effect of AG490（a JAK2/STAT5 inhibitor） on cytokines and their corresponding JAK2/STAT5 signal transduction pathway in bone marrow hematopoietic cells of myelodysplastic syndrome-refractory anemia MDS-RA. Methods After the method of detecting JAK2, STATS and Bcl-xL mRNA expression level was established by fluorogenic quantitative polymerase chain reaction （ FQ-PCR）, and JAK2, STATS, Bcl-xL signal transduction pathway was activated by granul stimulating factor （ GM-CSF ） in cultured bone marrow hematopoietic cells of 10 patients with MDS-RA, interleukin （IL）-2, IL-3, interferon-γ （IFN-γ）, tunor necro- sis factor-a（TNF-α） by enzym-linked immunosorbent assay （ELISA）and JAK2, STATS, Bcl-xL mRNA by FQ-PCR were measured between the AG490 group and the control group. Results IL-3, INF-γ level in the experiment groups was significantly lower than that in the control group （ P 〈 0.01 ）, and IL-2, TNF-α was similar to each other. The expression of JAK2, STAT5, Bcl-xL mRNA was signaificantly depressed in the experiment groups as compared with that in the control group （ P 〈 0.05 or P 〈 0.01 ）. Conclusions AG490 could modulate cytokines level of bone marrow hematopoietic cells of MDS-RA and then influence JAK2/STAT5 signal transduction,inhibit Bcl-xL mRNA expression.

关 键 词：骨髓增生异常综合征 AG490 信号转导 JAK2/STAT5 Bcl—xL 

分 类 号：R733.3[医药卫生—肿瘤]