再生障碍性贫血骨髓造血细胞遗传不稳定性的意义

目的 评价再生障碍性贫血(AA)患者骨髓造血细胞遗传不稳定性,探讨其对患者免疫抑制治疗(IST)的影响和在晚期克隆性血液学异常发生中的意义.方法 采用彗星试验检测AA患者骨髓造血细胞遗传不稳定性,分析其与反映骨髓造血衰竭参数的相关性,评价遗传不稳定对IST近期疗效的影响及IST对骨髓细胞遗传不稳定性的影响.结果 AA患者骨髓造血细胞彗星参数尾矩(TM)、Olive尾矩(OTM)、彗星细胞率(Comet%)均明显高于对照组(P值均<0.05);患者年龄、性别和外周血细胞计数与骨髓造血细胞各项彗星参数无相关性(P值均>0.05);比较Comet%<21.64%组与Comet%321.64%组、OTM<1.58组与OTM≥1.58组重型从(SAA)患者IST后6个月治疗反应差异无统计学意义(P>0.05);IST治疗对SAA患者彗星参数无明显影响,获得部分治疗反应者Comet%、TM、OTM以及获得完全治疗反应者Comet%均较治疗前明显降低.2例SAA患者在发生克隆性细胞遗传学异常前彗星参数均明显增高.结论 遗传不稳定性增高与骨髓造血衰竭可能是AA同一病理生理机制导致的不同表现形式;治疗前造血细胞遗传不稳定性对SAA患者IST近期疗效无影响;IST可能减轻获得治疗反应者骨髓造血细胞遗传不稳定.

The significance of hematopoietic cell genetic instability in aplastic anemia

Objective To evaluate bone marrow hematopoietic cells genetic instability (BMHCGI) in patients with aplastic anemia(AA) and to explore its influence on immunosupressive therapy for AA and significance on late clonal hematologic disorders.Methods Genetic instability of bone marrow mononuclear cells (BMMNC) was measured by Comet assay.The relationship between bone marrow failure parameters and genetic instability results was evaluated.The reciprocity of genetic instability and treatment responses to im-munosuppressive therapy (IST) was investigated.Results Comet assay parameters [tail moment (TM) , ol-ive TM(OTM), comet % ] of AA patients were significantly higher than that of control group (P<0.05).There was no statistic correlation of comet parameters of severe AA(SAA) BM hematopoietic cells with age, gender and peripheral blood cell count (P>0.05).For the treatment response rate at six months after IST there was no statistical difference between comet cells of<21.64% and of ≥21.64% , and so did between OTM<1.58 and 1.58 in SAA patients.IST had no effect on SAA BMHCGI, whereas,the Comet% , TM and OTM in SAA PR patients and Comet% in CR patients were significantly decreased than those before treat-ment.Comet parameters of two SAA patients were significantly increased before the development of clonal cy-togenetic abnormalities.Conclusions Increased BMHCGI may be one of the elements in the pathogenetic mechanisms in AA.The genetic instability is irrelevant to the SAA patients overall response rate of IST at six months, but IST can alleviate the genetic instabilities in responded SAA patients.