Preliminary Analysis Of Myeloid Tumor-related Gene Mutations In 293 Acquired Aplastic Anemia

Background:Acquired aplastic anemia(AAA)is a bone marrow hematopoietic failure disease primarily mediated by immunity.The late clonal evolution of AAA is its most serious complication.About 10%-20%of AAA patients are in combined immunosuppression Long-term clonal disease occurs after treatment.At present,clonal hemopoiesis has been confirmed in AAA,and this clonal hematopoiesis has a significant correlation with somatic mutations.We speculated that some patients with AAA have some myeloid tumor-related mutations,and may Age,gender,and severe classification at the first diagnosis are related,which may affect the prognosis of the disease.Objective:We analyzed the association of 25 myeloid tumor-related genes with age,gender,the severe classification,and results of immunosuppressive therapy(IST)in patients with AAA,so as to provide a possible basis for the hierarchical diagnosis of aplastic anemia.Method:We collected clinical data of 293 patients with AAA who visited the outpatient and inpatient department of the Children's Hospital of Suzhou University and the Jiangsu Provincial People's Hospital from September 2014 to October 2018,and used next-generation gene sequencing technology to detect 25 myeloid tumor genes,and divided patients into mutation group and non-mutation group.After a 6 months follow-up,the relationship between efficiency of IST and age,gender,gene mutation was evaluated.Results:1.Somatic mutations of myeloid tumor-related genes are present in 6.48%(19/293)of the patients.The variants occurred in ten genes:ASXL1(n=2),KRAS(n=1),PIGA(n=2),TP53(n=2),BCOR(n=2),TET2(n=5),SF3B1(n=1),DNMT3A(n=2),SH2B3(n=2),MPL(n=1).2.The gene with the highest mutation frequency was TET2.The main amino acid changes caused by the gene mutation were:p.G1137S and p.G1137fs.3.The mutation rate was similar between the male and the female,3.87%(6/155)vs 9.42%(13/138)(?2=3.71,P=0.05).4.The mutation rate in the children and adolescents group was 2.82%(4/142);9.93%(15/151)in the adult group,which was significant higher in the adult group(?2=6.11,P=0.01<0.05).5.The mutation rate was similar between the non-severe aplastic anemia(NSAA)and severe aplastic anemia group(SAA),7.87%(14/178)vs 4.35%(5/115)(?2=1.43,P=0.23>0.05).6.The responding rate at 6 months after IST between the mutant group and the non-mutated group was similar,73.68%(14/19)vs 63.11%(65/103)(?2=0.84,P=0.36>0.05).7.The responding rate at 6 months after IST between patients with or without TET2 mutant was similar,73.68%(14/19)vs63.11%(65/103)(?2=0,P=1>0.05).8.The responding rate at 6 months after IST among different mutation style groups was similar(Fisher>0.05).Conclusion:1.The mutation rate of 25 myeloid tumor-related genes in 293 AAA patients was 6.48%.2.The incidence of myeloid tumor-related somatic mutations was less in children than adult.3.The responding rate at 6 months after IST between the mutant group and the non-mutated group was similar.