摘要
目的观察初诊低危骨髓增生异常综合征(MDS)患者血红素加氧酶-1(HO-1)表达水平的变化及其基础水平与患者预后的关系,探讨HO-1在该病中可能的作用机制和临床应用前景。方法收集60例初诊低危MDS患者以及20例缺铁性贫血(IDA)患者的骨髓单个核细胞(BMMNCs),予不同浓度(0、5、10、20μM)的HO-1诱导剂Hemin体外孵育,用蛋白免疫印迹法检测HO-1蛋白表达水平和MAPK信号通路中c-Jun氨基末端激酶(JNK)磷酸化表达水平的变化,并随访分析HO-1的基础表达水平与患者无进展生存期(PFS)的关系。结果①低危MDS患者BMMNCs中HO-1蛋白基础表达水平与IDA患者比较差异无统计学意义(P>0.05);随着Hemin干预浓度的增加,HO-1蛋白表达量逐渐升高,JNK信号分子磷酸化表达水平亦逐渐升高,呈浓度依赖性(均为P<0.05);②HO-1高表达的患者PFS长于低表达患者组(中位数41.6个月vs.32.0个月,P=0.047)。COX回归分析显示HO-1表达水平是判断低危MDS患者预后的独立因素(P=0.006)。结论在低危MDS患者中,HO-1高表达者预后较好,HO-1可能通过JNK信号分子途径影响MDS的疾病过程。上调HO-1有可能成为改善疾病预后的新的治疗靶点。
Objective To investigate the relationship between the expression level of heme oxygen-ase-1 （HO-1 ）and the prognosis of lower-risk myelodysplastic syndromes （MDS）patients,and to explore the possible mechanism and clinical significance that HO-1 may involve.Methods Sixty newly diagnosed low-risk MDS patients and twenty iron deficiency anemia （IDA）patients were enrolled in this study.Isolated bone marrow mononuclear cells （BMMNCs）were cultured in the presence or absence of Hemin （inducer of HO-1 ） at different final concentrations of 5,1 0,20 μMfor 48 h.Western blotting were performed to detect HO-1 ex-pression and the activity of c-Jun N-terminal kinases （JNK）in BMMNCs.The relationship between HO-1 ex-pression levels and duration of progression-free survival （PFS）were further analyzed.Results ①No signifi-cant difference in HO-1 expression was observed between the low-risk MDS patients and the IDA patients （P〉0.05）.After treated with different concentrations of Hemin,HO-1 and phosphorylated JNK （p-JNK）expres-sion levels of BMMNCs increased gradually in a dose-dependent manner （P〈0.05）.② The median duration of PFS of patients with higher expression level of HO-1 was significantly longer than those with lower expression level of HO-1 （41 .6 months vs.32.0 months,P=0.047）.COX regression showed that HO-1 was an inde-pendent prognostic factor （P=0.006）.Conclusion High expression of HO-1 in low-risk MDS is associated with good prognosis,JNK signaling pathway might be involved in the effect of HO-1 on the progress of MDS, Up-regulation of HO-1 may be a new way to improve the prognosis of MDS.
出处
《新医学》
2014年第2期99-103,共5页
Journal of New Medicine
基金
山东省科技攻关基金(2006GG3202047)
山东省优秀中青年科研奖励基金(BS2009YY049)
