骨髓增生异常综合征患者骨髓CD34^-和CD34^+细胞凋亡与增殖的意义及对生存的影响(英文)  

Significance of CD34^- and CD34^+ Cell Apoptosis and Proliferation in Bone Marrow of Patients with MDS and Their Impact on Survival

作　　者：夏冰[1] 郭青[1] 赵丹丹[2] 赵海丰[1] 韩晓蘋[3] 王卉 吴晓雄[2] 张翼鷟[1] 

机构地区：[1]天津医科大学附属肿瘤医院血液科,天津市肿瘤防治重点实验室,天津300060 [2]解放军总医院第一附属医院血液科,北京100037 [3]解放军总医院血液科,北京100853 [4]北京市道陪医院,北京100037

出　　处：《中国实验血液学杂志》2012年第6期1392-1397,共6页Journal of Experimental Hematology

基　　金：supported by grants from the National Natural Science Foundation of China(30672208)

摘　　要：本研究分析骨髓增生异常综合征(MDS)患者骨髓CD34+和CD34-细胞凋亡和增殖情况,探讨MDS的发病机制,并判断其与疾病预后的关系。流式细胞术分析20例高危MDS、20例低危MDS患者及10例正常对照者骨髓CD34+细胞的比例、CD34+细胞和CD34-细胞凋亡、增殖的百分率,计算各组中的凋亡/增殖(A/P)比。并用单变量和多变量生存分析法分析CD34+细胞和CD34-细胞增殖和凋亡对预后的影响。结果表明:①MDS高危组患者骨髓CD34+细胞的比例明显高于低危组(P<0.05),而低危组与对照组比较无显著差异;②CD34+,CD34-细胞的凋亡率在MDS低危组中均为最高,明显高于MDS高危组和对照组。在低危组中,CD34-细胞的凋亡率为(80.36±1.82)%,明显高于CD34+细胞的(54.75±2.18)%(P<0.05),而在高危组中,CD34+,CD34-细胞的凋亡率无显著差异;③CD34+细胞的增殖率在MDS高危组中最高,明显高于低危组和对照组,而CD34-细胞的增殖率在MDS高危和低危组间无显著差异。高危组CD34+细胞的增殖率为(50.67±3.37)%,明显高于CD34-细胞的(30.99±1.96)%(P<0.05);④CD34+、CD34-细胞的A/P值在MDS低危组均明显高于高危组和正常对照组,而CD34-细胞的A/P值在MDS高、低危组均明显高于CD34+细胞的A/P值(P<0.05)。此外,CD34+细胞的凋亡率与生存及预后明显相关。结论:CD34+细胞百分率随MDS危险度增加而逐渐增加,在低危组中以CD34-细胞的凋亡占主导,随着病情进展,在高危组中则以CD34+细胞的增殖占主导,提示异常的凋亡和增殖在MDS的发生和发展中起重要作用。此外,CD34+细胞的凋亡率可能是独立的预后不良因素,抑制凋亡可能诱导MDS向白血病的转化。Alteration in the balance between cell apoptosis and proliferation is one of the pathophysiological mechanisms of the myelodysplastic syndromes （MDS）. The question of whether the excessive apoptosis and/or proliferation predominantly involve the subset of progenitor cells （CD34 ＋ cells） or mature cells （CD34- cells） remains a controversial issue. This study was purposed to analyze the apoptosis and proliferation status of CD34＋ and CD34 = cells in bone marrow（BM） of patients with MDS, to investigate the pathogenesis of MDS and to determine the relation of apoptosis and proliferation status of CD34＋ and CD34 - cells with prognosis of MDS. The proprotion of CD34＋ cells, the apoptosis and proliferation ratio （A/P） of CD34＋ and CD34- cells in BM of 40 patients with MDS, including 20 cases of high-risk MDS and 20 cases of low-risk MDS, and 10 normal persons as control were detected by flow cytometry; the influence of CD34＋ and CD34- cell apoptosis and proliferation levels on prognosis of MDS was evaluated by unvariate and multivariate analysis of survival. The results showed that the proportion of CD34＋ cells in BM of high-risk MDS patients was significantly higher than that in BM of low-risk MDS patients and in normal BM （1.92 ＋0.10）%, （1.09 ±0.04）%, （1.03 ±0.05）% respectively]. The apoptotlc rates （AR） of both CD34＋ and CD34 - cells were significantly higher in low-risk MDS [ （54.75 ±2.18） %, （80.36±1.68） % 3 than in high-risk MDS [（24.87 ±2.69）%, （23. 12 ±1.23）%1 and in normal BM [（18.51 ±2.74）%, （20.98±2.21）%]. When compared between CD34＋ cells and CD34 - cells in low-risk MDS, a greater AR of CD34 - cells was found. However, the higher proliferative rate of CD34＋ cells was observed in high-risk MDS. In low-risk MDS, a higher A/P ratio was found in CD34- cells than in CD34＋ cells; whereas this ratio was equalized or inverted in high-risk MDS. In addition, the survival and prognosis correlated significantly with AR of CD34�

关 键 词：骨髓增生异常综合征 CD34+细胞 CD34-细胞 细胞凋亡 细胞增殖 生存 预后因素 

分 类 号：R551.3[医药卫生—血液循环系统疾病]