Study On The Relationship Between Wilms’ Tumor 1 Gene Expression And Prognosis Of Myelodysplastic Syndromes

Background and objectivesMyelodysplastic syndromes(MDS)are heterogeneous myeloid hemopathies characterized by clonal disorders of hematopoietic and progenitor cells,leading to ineffective hematopoiesis,cytopenia,and an increased risk of evolution to acute myeloid leukemia.Patients’ survival varied widely between different disease subgroups and risk stratification.Predicting prognosis accurately is important to guide individualized treatment for MDS patient.Genetic defects play a major role in pathogenesis of MDS,so combining with information related to genetic defects could perfect prognostic assessment.Encoding a transcription factor that regulates cell growth and differentiation,Wilms’ Tumor 1(WT1)gene is a "pan-leukemic gene" and its expression level changes dynamically during normal hematopoiesis.Overexpression of WT1 gene is frequently observed in MDS,which indicates a poor prognosis.However,it is not clear whether the expression level of WT1 gene is related to different subtypes of MDS and leukemia transformation,and whether other molecular abnormalities affect the WT1 expression and its prognostic role.Therefore,this study retrospectively analyzed the association of WT1 gene expression with the prognosis of MDS,and further explored the clinical significance of WT1 gene expression while considering cytogenetic abnormalities and gene mutations.Methods1.In the first part,the clinical data of 225 patients with newly diagnosed MDS in Nanfang Hospital of Southern Medical University were retrospectively analyzed.The expression of WT1 gene in bone marrow was detected by real-time quantitative polymerase chain reaction(qRT-PCR)to explore the association of WT1 gene expression with MDS subtypes and IPSS-R scores.According to its expression level,all patients were divided into WT1 and WT1-group,their clinical characteristics and prognosis were compared.2.In the second part,a total of 215 patients with primary MDS who conceived qRT-PCR to detect WT1 gene expression,second-generation sequencing to detect gene mutation and chromosome banding technique to detect karyotype were included.This part retrospectively analyzed the relationship between WT1 gene expression and pre-existing prognostic factors like cytogenetic abnormalities and gene mutations to further explored the prognostic role of WT1 gene expression in different genetic backgrounds.Results1.WT1 gene expression was positively correlated with WHO 2016 classification and IPSS-R stratification.The higher the malignant degree of MDS subtypes and the risk stratifications of IPSS-R,the higher expression level of WT1 In addition,the level of WT1 gene expression can be used to differential diagnose MDS from other non-MDS-related hemocytopenia diseases.Compared with WT1-group,WT1+patients had shorter overall survival(OS)and higher risk of leukemia transformation.Among WT1+ patients,prognosis in those who under transplantation was significantly better than of patients with reduced cell therapy,immunotherapy or supportive therapy,along with the mortality was lower.2.WT1 gene expression was affected by other gene mutations,with decreasing WT1 expression was found in MDS patients with TP53,SRSF2,U2AF1,TET2 or CD101 mutations,while NPM1 mutated patients possessed higher expression.Notably,WT1 overexpression maintained its inferior prognostic effect on OS in TP53-wild patients but not in TP53-mutated group.In multivariate analysis,higher WT1 expression was one of the risk factors for OS in EB patients without TP53 mutations.ConclusionsWT1 gene expression level can be used to reflect the disease progression of MDS,which is closely related to the prognosis of MDS patients.Transplantation can improve the prognosis of WT1 overexpression patients.The expression level of WT1 was affected by some gene mutations,so considering gene mutation information can improve the prognostic role of WT1 gene expression to predict the prognosis of MDS patients accurately.