骨髓增生异常综合征患者血红素加氧酶表达水平及其临床意义

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）；② HO-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.