The High-throughput Next-generation Sequencing In The Antidiastole Of Hypoplastic Myelodysplastic Syndromes And Aplastic Anemia

Objective:Myelodysplastic syndromes are clonal disorder of hematopoietic stem cells,whereas some cases spresent a decreased bone marrow cellularity,which defined as hypodysplastic myelodysplastic syndromes.There are little characteristic in clinical manifestations and laboratory results between hypo-MDS and AA Which makes differential diagnosis hard.NGS has made great progress in recent years.In our study,we aimed to explore the significance of NGS in the clinical diagnosis and antidiastole between hypo-MDS and AA.Methods:We will use a 25-gene pannel which associated with MPN/MDS to sequence47 cases of BMFs including 22 cases of hypo-MDS and 25 cases of AA,treated in Guangzhou First People’s Hospital from January 2018 to August 2019,and a retrospective analysis combined Clinical features was carried out.Results:(1)The mutation frequency of Hypo-MDS patients was 59.10%(13/22),and the mean number of mutations per case was 1,and the common mutations were SETBP1、ASXL1、U2AF1、TP53in Hypo-MDS group.(2)The frequency of gene mutations was 60% in 15 hypo-MDS patients with normal cytogenetics,and the mean number of mutations per patient was 0.9333(0～5).(3)Four of 22 cases with AA(16%)had at least one mutation,the mean number of mutations per subject was 0.2,and there were five gene mutations identified by NGS in AA group,including DNMT3A、ASXL1、BCOR/BCORL1、RUNX1、U2AF1.(4)The mean number of mutations per case was higher in hypo-MDS compare with AA(P=0.002).(5)The frequency of mutations of hypo-MDS were higher than those of AA(P=0.002).(6)U2AF1、DNMT3A、ASXL1、BCOR/BCORL1 mutations were detected in both the hypo-MDS and AA groups,except for the ASXL1,there are higher VAF per mutation in hypo-MDS group.(7)On the basis of morphology and cytogenetics,four patients failed to meet the MDS diagnostic criteria.All of them found clonal mutations through NGS.Significantly higher number of mutations per case and frequency of mutations in hypo-MDS compare with AA(P = 0.001 、0.003,respectively),and the burden of mutations was higher in the cases(VAF range from 4.89% to 99.73%).Conclusion:These results suggest that the characteristic of mutation gene、 number of mutation genes per patient、 frequency of gene mutation and so on are different between AA and hypo-MDS.Thus,when hypo-MDS has been difficult to distinguish from AA,the NGS can provide strong molecular evidence.