Correlation Between Molecular Genetics And Clinical Features Of 77 Patients With Myelodysplastic Syndromes

[Objective]:To study the gene mutation spectrum and the clinical value of targeted Next-generation sequencing in de novo myelodysplastic syndromes.[Background]:Myelodysplastic syndromes(MDS)are a heterogeneous group of malignant clonal diseases which originate from multiple hematopoietic stem cells and characterized by abnormal development of hematopoietic cells,ineffective hematopoiesis,and accompanied by varying degrees of blood cell reduction,clonality chromosomal abnormalities and a high risk of transformation to acute myeloid leukemia(AML).Multiple-step genetic processes of somatic cells contribute to the occurrence and development of MDS.During this process,the activation of abnormal tyrosine kinase pathways caused by somatic driven gene mutations can lead the bone marrow hematopoietic stem cells to proliferate excessively and this is the beginning of bone marrow clonal hematopoiesis.It is well-known that the subtypes of MDS are diverse and the prognosis is variable.The difficities to diagnose and treat MDS are:1.to discriminate MDS among cytopenias and clonal hematopoiesis early;2.to divide MDS subtypes precisely and monitor disease dynamiclly;3.to evaluate reaction after chemotherapy or hemapoietic stem cell transplantation and monitor the evidence of early disease recurrence.Since these years,science and technology have been improved deeply and widely,the flow cytometry and advanced subjects such as cytogenetics have been provided technical support for the precise treatment and the division of the MDS subtypes.However,as the strong heterogeneity of MDS,it is not satisfied to understand the biological behavior of MDS.In terms of the classification of MDS subtype,the personalized accurate treatment,the prediction of prognosis and early relapse,there is still lots of work to do.As the occurance of high-throughput sequencing technology,the characteristics of MDS have been revealed extremely at the molecular biology level.Incorporating molecular biological markers into the parameters of standardized treatment is an irresistible trend.Some specific molecular biological markers are recognized having specifical association with the subtype of MDS,but there is still a lack of much clinical data to guide the diagnosis,subtyepes and clinical therapy.[Methods]:From June 2016 to July 2019,total of 77 newly diagnosed MDS patients were hospitalizated to the secondary affiliated hosptial of Soochow university,and enrolled to this study.Collecting general clinical characteristics,lab prolifies(including blood routine,bone marrow cell morphology,cytogenetics,and immunologic phenotype etc).Next-generation sequencing(NGS)were used to detect gene mutations in patients,and the relationship between molecular genetics and clinical stage,prognostic scores,and clinical characteristics of patients was analyzed.Based on the High-throughput sequencing.we analyse the relationship between molecular genetics and clinical stage,prognostic scores,and clinical characteristics of patients.[Results]:Among all petients,71(92.2%)patients were found with at least one mutaiton.The tope five mutations are U2AF1(26.0%)、AXSL1(23.4%)、TET2(19.5%)and DNMT3A、TP53(16.9%).About 34.3%of mutations are related to epigenetis change.29(37.6%)patients who have changed in three or more genetic functions groups are more likely to have a blast type(EB1+EB2)(P=0.0057).Coexistence of>/=3 mutations are frequent among patients who have high IPSS-R Scores(>4.5分)which means these patients may have bad prognise(P=0.0386).[Conclusion]:The number of gene mutations and function aberration in patients with MDS will affect the subtype classification,prognostic score and clinical characteristics of the disease.This study found that patients who bear 2 or more gene mutations tend to have a poorer disease subtype(EB1+EB2);patients who changed at least 3 kinds of gene mutation functional groups had higher IPSS-R scores(>4.5 points).Clinically,patients who have these two characteristics should be paid more attention.Molecular biology changes should be used as one of the parameters for individual management and treatment of MDS.