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

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。

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

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＋cells. It is concluded that the early MDS is predominantly associated with excessive apoptosis of the mature CD34- cells. The proliferation rate of cells increases with the disease progression in MDS subsets, especially, in the subset of CD34 ＋ cells. Surprisingly, the apoptosis of CD34＋ cells may be a useful prognostic factor, and the inhibition of apoptotic mechanisms may induce the transformation of MDS to leukemia.