METHODS: In this study, the concentrations and fragment distributions of plasma cfDNA were preliminary investigated in elderly (n = 1) and paediatric (n = 1) patients with acute promyelocytic leukaemia (APL) treated with arsenic trioxide (ATO).
RESULTS: A slight increase in cfDNA concentrations was observed in the APL patients compared with healthy controls. The change in plasma cfDNA concentrations corresponded to the change in plasma arsenic concentrations during ATO treatment. The fragment distribution pattern did not differ before and during treatment. Three ladder fragments were observed in part of the cfDNA in the second consolidation therapy in an elderly APL patient and the first consolidation therapy of a paediatric APL patient, while two fragments were observed in all other treatment periods. Moreover, APL-related gene mutations were successfully genotyped from plasma cfDNA by using polymerase chain reaction-based methods and these results are consistent with those from leukocytes.
CONCLUSIONS: This study is the first to report the concentrations and fragment patterns of cfDNA from APL patients treated with ATO. The results suggested that plasma cfDNA concentration in APL patients increased with ATO treatment and that cfDNA is released mainly via neutrophil extracellular traps (and/or necrosis) in addition to apoptosis. To confirm whether cfDNA concentrations and fragment patterns can be used as a biomarker for APL treated with ATO, further accumulative data are needed.
方法:在本研究中,在接受三氧化二砷(ATO)治疗的老年(n=1)和儿科(n=1)急性早幼粒细胞白血病(APL)患者中,初步研究了血浆cfDNA的浓度和片段分布。
结果:与健康对照相比,在APL患者中观察到cfDNA浓度略有增加。血浆cfDNA浓度的变化对应于ATO治疗期间血浆砷浓度的变化。片段分布模式在治疗前和治疗期间没有差异。在老年APL患者的第二次巩固治疗和儿科APL患者的第一次巩固治疗中,在cfDNA的部分中观察到三个阶梯片段,而在所有其他治疗期间观察到两个片段。此外,通过使用基于聚合酶链反应的方法,成功地从血浆cfDNA中对APL相关基因突变进行了基因分型,这些结果与白细胞的结果一致。
结论:这项研究首次报道了用ATO治疗的APL患者的cfDNA浓度和片段模式。结果表明,ATO治疗后,APL患者的血浆cfDNA浓度增加,除凋亡外,cfDNA主要通过中性粒细胞胞外陷阱(和/或坏死)释放。为了确认cfDNA浓度和片段模式是否可以用作ATO治疗APL的生物标志物,需要进一步积累数据。