Study On The Correlation Between U2AF1 Gene Mutation Characteristics And Prognosis In Patients With Myelodysplastic Syndrome

Background:Myelodysplastic syndromes(MDS)are a group of clonal hematopoietic stem cell diseases with a heterogeneous spectrum of ineffective hematopoiesis,refractory blood cell reduction and rapidly developing to acute myeloid leukemia(AML).With the rapid development and widespread use of the next generation sequencing(NGS)technology in the past decade,many gene mutations have been founded in MDS patients.In addition,studies have shown that several gene mutations are strongly associated with prognosis in patients with MDS.U2AF1 is one of the most common mutated genes in MDS.However,the clinical features of U2AF1 mutations and their relationship with prognosis vary from center to center.This study retrospectively analyzed the U2AF1 gene mutation characteristics and its effect on prognosis in 271 MDS patients who underwent NGS,to determine the prognosis of these patients and guide treatment.Methods:This retrospective study examined patients who diagnosed with myelodysplastic syndromes at Nanfang Hospital,Southern Medical University between April 1st 2012 and October 31st 2019.All patients were diagnosed by bone marrow morphology,immunotyping,cytogenetics,molecular biology and bone marrow biopsy.Data were reclassified according to the Chinese Guidelines for Diagnosis and Treatment of Myelodysplastic Syndrome(2019).A total of 271 MDS patients underwent NGS were included.According to whether the patients have U2AF1 gene mutation,the patients were divided into U2AF1 mutation group and wild-type group,and the relationship between gene mutation characteristics and clinical manifestations and prognosis was analyzed in the two groups.Then according to the difference of the mutation site of U2AF1,the patients in U2AF1 group were divided into U2AF1S34 mutation group and U2Ar1Q157/R156 mutation group,anA the clinical characteristics and prognostic impact were analyzed of the patients in the two groups.All statistical analyses were performed by using the statistical software package SPSS Version 23.0,and considered p-values of less than 0.05 to be statistically significant.Differences between numerical variables were calculated by means of Mann-Whitney U test,pearson Chi-square analysis and Fisher exact test were used to compare groups for non time-to-event categorical variables.Survival curves were generated by the Kaplan-Meier test and survival was compared using the log-rank test.Results:(1)The incidence of U2AF1 mutation in MDS patients in our hospital was 11.4%(31/271),and the mutation sites were mainly located in S34 and Q157.(2)There were significant differences between U2AF1 wild-type group and U2AF1 mutation group in the gender and the bone marrow blasts(P=0.001 and P=0.027 respectively).The risk of cytogenetics and IPSS-R risk stratification in the U2AF1 mutant group was lower than that in the U2AF1 wild group(P=0.038 and P=0.036 respectively).There was no patient has complex karyotypes and TP53 gene mutation in the U2AF1 mutation group and compare to U2AF1 wild-type group,there were significant differences in complex karyotypes and TP53 gene mutation(P=0.004 and P=0.019 respectively).There were no significant differences in ages,blood parameters,WHO 2016 classification,IPSS-R category,common chromosomal abnormalities like del(5q),-7/del(7q),del(20q),+8 and common gene mutation like TET2,ASXL1,TET1,EZH2,RUNX1,SF3B1,DNMT3A,SRSF2,ZRSR2 mutation between the U2AF1 mutation group and the wild-type group.(3)The median age at diagnosis of U2AF1S34 patients was lower than that of U2AF1Q157/R156 patients(P=0.031).No differences were observed in gender,WHO 2016 classification,IPSS-R category and blood parameters between U2AF1S34 and U2AF1Q157/R156 mutation group.(4)There was no significant difference in the overall survival time(P=0.781)and the time of acute myeloid leukemia(AML)transformation(P=0.787)of MDS patients with U2AF1 wild-type,U2AF1S34 mutation and U2AF1Q157/R156 mutation,as well as in the lower risk group and the higher risk group.U2AF1 mutation does not affect the response to hypomethylating agents in MDS patients(P=0.484).There was no significant difference in the overall survival time of MDS patients who only received chemotherapy with U2AF1 wild-type,U2AF1S34 mutation and U2AF1Q157/R156 mutation(P=0.182),so as in the lower risk group and the higher risk group of IPSS-R risk stratification.No statistically significant difference was observed in overall survival time between patients with and without U2AF1 mutation in the transplant group(P=0.169).Conclusion:The results of this study suggested that,compared with patients without U2AF1 mutation,the proportion of male patients with U2AF1 mutation was higher,the bone marrow blasts were relatively low at first diagnosis,and there was no complex karyotype in U2AF1 mutation group.The U2AF1 gene mutation did not affect the survival time,AML transformation time,and response rate to hypomethylating agents in MDS patients.Besides,Except that the median age at diagnosis of U2AF1S34 patients was smaller than that of U2AF1Q157/R156 patients,no statistically significant differences in clinical characteristics and prognosis were observed between these two mutation sites.Since this study was a single-center retrospective study,U2AF1 gene mutation characteristics and its effect on prognosis need to be verified in a large sample.