| Objective:In recent years,MDS-related gene mutations have become a research hotspot.The purpose of this study was to detect the common types of gene mutations in MDS patients in our unit,and discover the relationship between gene mutations and the clinical features of MDS and their impact on the prognosis.Methods:A total of 221 patients who were hospitalized in the Department of Hematology,Affiliated Hospital of Qingdao University for the detection of gene mutation of newly diagnosed MDS from September 1,2010 to September 1,2020 were analyzed retrospectively,including 125 patients with positive gene mutation detection and 96 patients with negative gene mutation detection.The clinical data were collected and divided into gene mutation positive group and gene mutation negative group.The disease was diagnosed according to the Chinese Guidelines for Diagnosis and Treatment of Myelodysplastic Syndromes(2019 edition).The disease diagnosis of the above patients was classified according to the revised classification of MDS 2016 WHO,and the prognosis was evaluated according to the revised International Prognostic Score System for MDS(IPSS-R).All statistical analyses were performed using SPSS 22.0 statistical software.Chi-square test or Fisher exact test was used for comparison between the gene mutation positive group and the gene mutation negative group,Kaplan-Meier method was used for survival analysis,log-rank test was used for univariate analysis,and Cox regression model was used for multivariate analysis.P < 0.05 indicated that the difference was statistically significant.Results:1.The incidence of all gene mutations was 56.6%(125/221);the relationship between the gene mutation and clinical features of MDS patients showed that the gene mutation was significantly correlated with gender,hemoglobin,number of bone marrow blasts,peripheral cytopenia lineage,WHO(2016)classification,IPSS-R hierarchical grouping,and cytogenetics of MDS patients(P < 0.05).2.Among the 125 MDS patients in the gene mutation positive group,32%(40/125)of them developed one gene mutation,24%(30/125)of them had two gene mutations,20%(25/125)of them had three gene mutations,10.4%(13/125)of them had four gene mutations,6.4%(8/125)of them had five gene mutations,4.8%(6/125)of them had six gene mutations,and 2.4%(3/125)of them had seven gene mutations.The top ten mutated genes in 125 MDS patients in the gene mutation positive group were KMT2D(7.71%),ASXL1(7.10%),JAK2(5.86%),U2AF1(4.63%),RUNX1(4.63%),TET2(4.63%),SETBP1(4.32%),DNMT3A(4.32%),EZH2(4.01%)and SF3B1(3.70%),respectively.According to the functional classification of the genes,the percentages of epigenetic genes,clipper genes,signaling pathway genes,transcription factor genes,cell cycle and apoptosis genes,adhesion protein complex genes and other genes of undetermined significance were 41.05%,12.04%,20.68%,13.89%,3.09%,1.54% and 7.72%,respectively.3.In the gene mutation positive group,94 patients(75.2%)were alive(median survival time was 10months),21 patients(16.8%)were converted to AML,and 19patients(15.2%)died with a median survival of 10 months.Among them,10 patients(8%)died from MDS-related infection or multiple organ failure,and 9 patients(7.2%)died from conversion to AML.In the gene mutation negative group,16 patients(16.7%)were alive,26 patients(27.1%)were converted to AML,and 80 patients(83.3%)died with a median survival of 14.7 months.Among them,56 patients(58.3%)died from MDS-related infection or multiple organ failure,and 24 patients(25%)died from conversion to AML.4.Univariate survival analysis and log-rank test of genes with mutation frequency > 2% respectively showed that ETV6,MPL,NRAS,KIT and TP53 genes were significantly correlated with shorter OS(P < 0.05).5.Multivariate analysis using Cox model showed that the number of bone marrow blasts,cytogenetics,and gene mutation were the independent risk factors for the prognosis of MDS(P < 0.05).Conclusion:1.The gene mutations were significantly associated with gender,hemoglobin,number of bone marrow blasts,peripheral cytopenia lineage,WHO(2016)classification,IPSS-R stratification grouping,and cytogenetics of MDS patients(P<0.05).2.Compared with MDS patients in the gene mutation negative group,the positive gene mutation has an impact on the overall survival of MDS patients(P<0.05);in MDS patients with leukemia,positive versus negative gene mutations have an impact on the overall survival of MDS patients(P<0.05).3.Among 125 MDS patients in the gene mutation positive group,the top ten mutated genes in the detected patients were KMT2 D,ASXL1,JAK2,U2AF1,RUNX1,TET2,SETBP1,DNMT3 A,EZH2 and SF3B1.According to the functional classification of genes,the most common gene mutations were epigenetic mutations,namely,KMT2D、ASXL1、TET2、DNMT3A、SETBP1、EZH2、WT1、IDH1、EP300、IDH2、DNMT3B、SMCIA followed by RNA clipper mutation,namely,U2AF1、SF3B1、SRSF2、ZRSR2.4.Multivariate analysis showed that the number of bone marrow blasts,cytogenetics,and gene mutation were independent risk factors affecting the prognosis of MDS(P<0.05).5.Both univariate and multivariate analyses revealed that gene mutations(ETV6,MPL,NRAS,KIT,and TP53)were independent prognostic factors for MDS. |
