免疫抑制治疗对再生障碍性贫血患者骨髓细胞遗传不稳定性的影响

目的 研究强烈免疫抑制治疗(IST)对再生障碍性贫血(AA)患者骨髓细胞遗传不稳定性的影响.方法 采用彗星试验检测患者骨髓细胞遗传不稳定性,以彗星尾部DNA(TDNA)百分比、尾长(TL)、尾矩(TM)、Olive尾矩(OTM)和彗星细胞率作为分析参数,分别检测IST前后AA患者骨髓细胞,并与对照组结果比较.结果 91例初治从患者TDNA百分比、TL、TM、OTM、彗星细胞率分别为(5.0±4.0)%、11.3±7.2、1.7±2.0、1.5±1.4、(16.8±13.7)%,明显高于对照组(P值均<0.05);58例重型AA(SAA)与33例非重型AA(NSAA)患者彗星试验各项参数比较差异均无统计学意义(P值均>0.05),二组患者各彗星试验参数与对照组比较,差异均有统计学意义(P值均<0.05).53例SAA患者治疗后3个月TDNA百分比、TL、TM、OTM、彗星细胞率分别为(4.4±3.6)%、10.4±7.5、0.4±1.6、1.3±1.4、(20.2±21.2)%,30例SAA患者治疗后6个月TDNA百分比、TL、TM、OTM、彗星细胞率分别为(3.7±3.3)%、10.0±7.2、1.2±1.8、1.1±1.3、(18.5±19.0)%,结果与58例SAA患者IST前彗星参数比较差异均无统计学意义(P值均>0.05).结论 AA患者骨髓细胞存在遗传不稳定性,IST本身近期并不增加SAA患者细胞遗传不稳定性.提示IST与从患者发生晚期克隆性血液学异常可能无关.

The impact of immunosuppressive therapy on genetic instabilities of bone marrow hematopoietic cells in patients with aplastic anemia

Objective To investigate the impact of immunosuppressive therapy(IST) on genetic in-stabilities of bone marrow hematopoietic cells (BMHCs) in patients with aplastic anemia(AA). Methods Comet assay as used to detect genetic instabilities of hematopoietic ceils from patients, and the percent of DNA in comet tail (TDNA), tail length(TL), tail moment(TM), olive tail moment(OTM) and the rate of comet cells were measured. BMHCs from AA patients were examined with comet assay before and after IST, and the results were compared with those from controls. Results Comet parameters from 91 AA patients in-cluding TDNA, TL, TM, OTM comet cell percentage were (5.0 ± 4.0) %, 11.3 ± 7.2, 1.7 ± 2.0, 1.5 ± 1.4, (16.8 ± 13.7)%, respectively, which were significandy higher than those from control group (P < 0.05). There were statistical differences between the comet parameters of severe AA(SAA)/non-SAA (NSAA) and those of control group(P <0.05), but no difference in the comet parameters between SAA and NSAA patients(P>0.05). The TDNA, TL, TM, OTM and comet cells percentage were (4.4±3.6)%, 10.4 ± 7.5, 1.4 ± 1.6, 1.3 ± 1.4 and (20.2 ± 21.2) %, respectively at 3 months after [ST in 53 SAA pa-tients and were (3.7 ± 3.3) %, 10.0 ± 7.2, 1.2 ± 1.8, 1.1 ± 1.3 and (18.5 ± 19.0) % respectively at 6 months after IST in 30 SAA patients, being no statistical difference from those of 58 SAA patients before IST (P values were all > 0. 05). Conclusion B MHCs of AA had inherent genetic instabilities which were not increased by recent IST. It indicated that there was no correlation between LST and the development of clonal hematologic disorders in AA.