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目的探讨不同类型骨髓增生异常综合征(MDS)患者骨髓染色体核型和凋亡现象及其机制。方法采用骨髓短期培养和G显带技术对40例MDS患者进行染色体核型分析,钙磷脂结合蛋白(Annexin-Ⅴ)-FITC标记药物骨髓单个核细胞,了解其早期凋亡的情况,逆转录-PCR分析自杀相关因子(Fas)和凋亡抑制蛋白(survivin,生存素)mRNA表达变化。结果 20/40例MDS患者检出染色体异常,其中难治性贫血(RA)7/20例(35%),RA伴有环状铁幼粒细胞(RARS)1/2例(50%),RA伴多系发育异常(RCMD)5/8例(62.5%),RA伴原始细胞增多(RAEB)7/10例(70%);国际预后评分系统(IPSS)1年白血病转化率为低危组5%(1/20),中危1、2组25%(3/12),高危组75%(6/8),各组间差异有统计学意义(P<0.05);骨髓单个核细胞凋亡MDS患者高于10例正常体检者(对照组),从低危组到高危组凋亡减少,生存素基因mRNA表达增加,FasmRNA表达下降。结论染色体核型分析在MDS的预后评估中有重要价值;MDS从低危组到高危组凋亡减少,可能与生存素、Fas基因表达有关。
Objective To investigate the bone marrow karyotype and apoptosis in different types of patients with myelodysplastic syndrome (MDS) and its mechanism. Methods Chromosome karyotype analysis was performed in 40 patients with MDS using bone marrow short-term culture and G-banding technique. The drug-induced bone marrow mononuclear cells were labeled with Annexin-V-FITC to detect the early apoptosis and reverse transcription- PCR analysis of suicide-related factors (Fas) and apoptosis inhibitor protein (survivin, survivin) mRNA expression changes. Results Chromosomal abnormalities were detected in 20/40 patients with MDS, of which 7/20 (35%) were refractory anemia (RA) and 1/2 (50%) were associated with RA. 5/8 cases (62.5%) of RA with multiple lineage dysplasia (RCMD) and 7/10 cases (70%) of RA with blasteocytosis (RAEB). The 1 year leukemia conversion rate of International Prognostic Score System (IPSS) was low risk (1/20), 25% (3/12) in middle-risk group 1 and 2, and 75% (6/8) in high-risk group. There was a significant difference among the groups (P <0.05) Apoptotic MDS patients were higher than 10 normal subjects (control group). Apoptosis decreased from low-risk group to high-risk group, survivin mRNA expression increased and Fas mRNA expression decreased. Conclusion Chromosome karyotype analysis is of great value in the prognosis evaluation of MDS. The apoptosis of MDS from low risk group to high risk group may be related to survivin and Fas gene expression.