摘要目的 观察骨髓增生异常综合征(MDS)患者生长分化因子11(GDF11)的表达,分析其与红系造血功能的相关性.方法 选取2014年9月至2015年6月天津医科大学总医院血液内科MDS患者44例,其中低危组18例,高危组26例,采用酶联免疫吸附试验检测外周血GDF11的浓度、RT-PCR方法检测骨髓单个核细胞(BMMNC) GDF11基因mRNA的表达水平、流式细胞术检测MDS患者骨髓红系(CD235a)的百分比,并与10名健康对照做比较;分析上述变化与外周血红细胞计数(RBC)、血红蛋白(Hb)、红细胞比容(Hct)、平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)、平均红细胞血红蛋白浓度(MCHC)、网织红细胞(Ret)百分比、骨髓有核红细胞比例的相关性.结果 (1) MDS患者外周血GDF11的水平:高危组MDS患者外周血GDF11水平显著高于低危组[(128.67 ±47.62)比(65.96±36.55) μg/L,P＜0.01]和健康对照组[(29.76±10.10) μg/L,P＜0.01];低危组显著高于健康对照组(P＜0.05).中重度贫血MDS患者外周血GDF11水平高于正常和轻度贫血患者[(80.97±9.94)比(66.82±19.52) μg/L],但两组差异未达统计学意义(P＞0.05).(2) MDS患者骨髓CD235a的水平:高危组MDS患者骨髓单个核细胞CD235a的表达率为38.49％±5.42％,低危组为42.64％±7.36％,两组差异没有统计学意义(P＞0.05).(3)不同危险度MDS患者外周血GDF11水平与红系指标的相关性:高危组MDS患者外周血GDF11浓度与外周血Hb、RBC、Hct均呈负相关(r=-0.437、-0.430、-0.306,均P＜0.05),与骨髓有核红细胞比例、Ret百分比、MCV和骨髓CD235a的表达呈正相关(r=0.465、0.392、0.505、0.387,P＜0.05),与MCHC和MCH无相关性(均P ＞0.05).低危组MDS患者外周血GDF11浓度与骨髓CD235a的表达呈正相关(r=0.429,P＜0.05),与外周血Hb、RBC、Ret百分比、MCV、MCH、MCHC、Hct及骨髓有核红细胞比例均无相关性(均P ＞0.05).(4) RT-PCR方法检测GDF11基因的表达:MDS组GDF11 mRNA表达水平高于健康对照组(39.82±14.55比1.84±0.64),差异有统计学意义(P＜0.01).结论 MDS患者外周血GDF11水平高,且随着危险度升高而升高,贫血严重程度越高,GDF11水平越高,与MDS红系造血指标密切相关.

abstractsObjective To detect the expression level of growth differentiation factor 11 (GDF11) in patients with myelodysplastic syndrome (MDS),and to evaluate the relationship between GDF11 level and erythropoiesis functions.Methods A total of 44 MDS patients (18 low-risk group patients and 26 high-risk group patients) in Department of Hematology in Tianjin Medical University General Hospital and 10 normal controls were selected from September 2014 to June 2015.The concentration of GDF11 in peripheral blood was detected using enzyme-linked immunosorbent assay (ELISA).GDF11 mRNA expression in bone marrow mononuclear cells (BMMNC) was detected using RT-PCR method.The percentage of erythroid cells (CD235a) in bone marrow was detected by flow cytometry.The correlation between these indexes and erythropoiesis functions (including red blood cell count (RBC),hemoglobin level (Hb),hematocrit (Hct),mean corpuscular volume (MCV),mean corpuscular hemoglobin (MCH),mean corpuscular hemoglobin concentration (MCHC),reticulocyte percentage (Ret％),and proportion of nucleated eryhrocyte in bone marrow) were evaluated.Results (1) The GDF1 1 level in peripheral blood was significantly higher in high-risk group ((128.67 ±47.62) μg/L) than in low-risk group ((65.96 ±36.55) μg/L,P ＜0.01) and in normal controls ((29.76 ± 10.10) μg/L,P ＜ 0.01),also significantly higher in low-risk group than in normal controls (P ＜ 0.05).The concentration of GDF11 in severe/moderate anemic MDS patients ((80.97 ± 9.94) μg/L) was higher than that in normal controls/mild anemic MDS patients ((66.82 ± 19.52) μg/L),but with no statistically significant (P ＞ 0.05).(2) The percentages of CD235a+ cells in high-risk and low-risk groups were 38.49％ ± 5.42％ and 42.64％ ± 7.36％,respectively,showing no statistically significant difference (P ＞ 0.05).(3) In high-risk group,the GDF11 level in peripheral blood was negatively correlated with Hb,RBC and Hct in peripheral blood (r =-0.437,-0.430,-0.306,all P ＜ 0.05),and positively correlated with nucleated eryhrocyte,Ret％,MCV and CD235a + cells in bone marrow (r =0.465,0.392,0.505,0.387,all P ＜ 0.05),but not correlated with MCH and MCHC (both P ＞ 0.05).In low-risk group,the GDF11 level in peripheral blood was positively correlated with CD235a + cells in bone marrow (r =0.429,P ＜ 0.05),and not correlated with Hb,RBC,Ret％,MCHC,MCV,MCH,Hct and nucleated eryhrocyte (all P ＞0.05).(4) The mRNA expression of GDF11 in MDS patients (39.82 ± 14.55) was higher than that in the controls (1.84 ±0.64,P ＜0.01).Conclusions GDF11 level in peripheral blood is higher in patients with MDS and increases with the disease risk.The more severe the anemia,the higher the GDF11 level.It may be closely correlated with erythropoiesis indicators in MDS.