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免疫抑制治疗不增加再生障碍性贫血骨髓造血细胞遗传不稳定性

Immunosuppressive Therapy Does Not Increase Genetic Instabilities of Hematopoietic Cells in Patients with Aplastic Anemia

【作者】 张丽红

【导师】 张凤奎;

【作者基本信息】 中国协和医科大学 , 血液内科, 2007, 硕士

【摘要】 【目的】研究再生障碍性贫血(AA)患者骨髓造血细胞遗传不稳定性及强烈免疫抑制治疗(IST)对于从发生晚期克隆性血液学异常的影响。【对象和方法】采用彗星试验评价骨髓造血细胞遗传不稳定性,以彗星尾部DNA百分含量(TDNA%)、尾长(TL)、尾矩(TM)、Olive尾矩(OTM)和彗星细胞率(Comet%)作为分析参数,分别检测IST治疗前后从患者骨髓造血细胞,并与18例对照组结果比较。【结果】91例初治AA患者TDNA、TL、TM、OTM、Comet%分别为:5.02±3.95、11.25±7.19、1.70±2.02、1.50±1.38、16.84±13.65明显高于对照组(p<0.05);58例重症AA(SAA)与33例非重症AA(NSAA)患者彗星试验各项参数比较均无差别(p>0.05),二组患者分别与对照组比较,各彗星参数仍明显为高(p<0.05)。53例SAA治疗后3月患者TDNA、TL、TM、OTM、Comet%分别为:4.43±3.64、10.37±7.49、1.37±1.61、1.29±1.37、20.17±21.17,30例SAA治疗后6月患者TDNA、TL、TM、OTM、Comet%分别为:3.71±3.32、10.04±7.18、1.15±1.80、1.12±1.29、18.47±19.02,与58例IST治疗前SAA患者彗星参数结果比较均无差异(p>0.05)。18例SAA患者IST治疗前后均进行了彗星试验检测,彗星参数比较无统计学差异(p>0.05)。【结论】AA患者骨髓造血细胞存在遗传不稳定,免疫抑制治疗本身并不增加SAA患者细胞遗传不稳定性。提示免疫抑制治疗与AA发生晚期克隆性血液学异常可能无关。

【Abstract】 ObjectiveTo investigate the genetic instabilities of bone marrow hematopoietic cells from patients with aplastic anemia and evaluate the impact of IST in aplastic anemia evolving into clonal hematologic disorders.MethodsComet assay were used to evaluate the genetic instabilities of hematopoietic cells and the percent of DNA in the comet tail (TDNA%), tail length(TL), tail moment(TM) olive tail moment(OTM) and the rate of comet cells (Comet%) were selected as analyzing parameters. Bone marrow hematopoietic cells from patients with aplastic anemia examined with comet assay before and after IST separately, and the results were compared with those from 18 controls.ResultComet parameters from 91 patients with aplastic anemia including TDNA, TL, TM, OTM and Comet% were 5.02±3.95, 11.25±7.19, 1.70±2.02, 1.50±1.38 and 16.84±13.65 separately, all of which were obviously superior to those from control group respectively (p<0.05). The results were remained notablely higher when separately compared the comet parameters of SAA and NSAA with those of control group (p<0.05) , and there were no differences of the examined comet parameters of 58 SAA from those of 33 NSAA patients (p>0.05) .The parameters TDNA, TL, TM, OTM and Comet% were 4.43±3.64, 10.37±7.49, 1.37±1.61, 1.29±1.37 and 20.17±21.17 respectively 3-months later after IST in 53 SAA patients and those were 3.71±3.32, 10.04±7.18,1.15±1.80, 1.12±1.29 and 18.47±19.02 respectively 6-months later after IST in 30 SAA patients , which had no difference from those of 58 patients before IST (p>0.05) .There was no statistical difference in comet parameters of 18 SAA patients before and after IST (p>0.05) .ConclusionsBone marrow hematopoietic cells of aplastic anemia had intrinsic nature of genetic instabilities which were not seemed to be increased by IST. It may be impossible of IST being crucial in aplastic anemia evolving into clonal hematologic disorders.

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