Analysis Of Gene Mutations In Acute Myeloid Leukemia And Myelodysplastic Syndrome

Objective: To investigate the gene mutation of newly diagnosed AML(non-APL)and MDS,and to explore the clinical significance of gene mutation in AML and MDS.Methods:A total of 125 patients with AML(non-APL)and MDS were enrolled in the study,who were firstly diagnosed at Department of Hematology of the Second Hospital of Hebei Medical University and received the initial treatment detected by the second generation sequencing from October 2016 to January 2018.They were divided into two groups according to the type of disease.The incidence,types of mutation,distribution,mutations of genetic functional group were investigated among myeloid neoplasms with 22 common gene mutations in the above two disease types.The correlation between these gene mutations and clinical manifestations as well as the efficacy of standard chemotherapy regimen were analyzed statistically.Results:1.The frequency of gene mutation in the newly diagnosed AML group was 72.0%,of which 30.5% was accompanied by more than two gene mutations.The most common(mutation rate>10%)gene mutations were TET2(46.3%),CEBPA(17.1%)and FLT3(12.2%)successively based on the frequency.The frequency of gene mutation in the newly diagnosed MDS group was 69.8%,of which 37.2% was accompanied by more than two gene mutations.The most common(mutation rate>10%)genes were SF3B1(23.2%),U2AF1(16.2%),TET2(14.0%),ASXL1(11.6%)and DNMT3A(11.6%)successively based on the frequency level.2.AML gene mutations occurred mainly in epigenetic regulatory genes(68.3%),signaling pathway genes(31.7%)and transcription factor-related genes(28.0%).MDS gene mutations occurred mainly in spliceosome-associated genes(46.5%)and epigenetic regulatory genes(46.5%).In most cases,synergistic mutations occur in different functional groups.3.In newly diagnosed AML,TET2 gene mutation was associated with higher proportion of bone marrow blasts,while IDH1 mutation was associated with higher platelet count.KIT mutant was more common in the low risk group with chromosome karyotype.Patients with FLT3-ITD and TP53 mutations had poor response to chemotherapy.4.In newly diagnosed MDS,SF3B1 mutation was associated with older age,while ASXL1 mutation was more common in men and SF3B1 was more likely to appear in MDS-RARS.Patients with TET2 mutation had better response to chemotherapy.Conclusions:1.The incidence of AML and MDS gene mutations is different.Mutations vary among biological functional groups.In most cases,synergistic mutations of genes occur in different functional groups.2.Some gene mutations in AML and MDS are correlated with clinical manifestations.3.Gene mutation has a certain effect on the short-term clinical efficacy of myeloid neoplasms.The detection of gene mutation is of great significance to the establishment of individualized diagnosis and treatment regimen in clinical practice.