Analysis Of Genes And The Significance Of JAK3 Mutation In Adult Acute Lymphoblastic Leukemia

Part 1 Analysis of genes in adult acute lymphoblastic leukemiaObjectiveThe characteristics of gene distribution in adult acute lymphoblastic leukemia(ALL)were analyzed,and the prognostic characteristics of related genes were explored by the minimal residual disease detection(MRD).Materials and MethodsA retrospective analysis of 246 newly treated adult patients with acute lymphoblastic leukemia diagnosed in our hospital from January 2017 to December 2019,combined with flow cytometry,real-time fluorescence quantitative PCR(RT-PCR),and next-generation sequencing technology((NGS)detected leukemia immunotype and MRD,43 fusion genes and 16 mutant genes.SPSS 21.0 was used to statistically analyze the data.Count data were analyzed by χ 2 test.Survival analysis was performed by Kaplan-Meier test.P<0.05 indicated that the difference was statistically significant.ResultsAmong 246 ALL patients,202 were B-ALL patients and 40 were T-ALL patients.Among them,CD 19,cCD79a were the most diagnostic value in B-ALL,and cCD3 and CD7 were the most diagnostic value in T-ALL.RT-PCR detected a total of 99(40.2%)patients expressing 8 fusion genes,9(44.6%)patients expressed fusion genes in 90 patients in B-ALL,and the three higher expressions were:BCR-ABL(75 Example),E2A-PBX1(10 cases),MLL-AF4(5 cases).NGS detected a total of 69(28.0%)patients expressing 12 mutant genes,28(70%)patients patients had genetic mutations in T-ALL,and 48.3%of patients had co-mutation.The higher mutation rates in T-ALL are:NOTCH1,JAK3,FBXW7,and IL-7R;the higher mutation rates in B-ALL are:TP53,IL-7R,and PAX5.Many signal pathways involved in this study include JAK/STAT signal pathway(JAK1,JAK3,IL-7R),NOTCH signal pathway(NOTCH1,FBXW7),and MARK/PI3K signal pathway(TP53).Patients with mutations in E2A-PBX1 gene and JAK/STAT signaling pathway had higher MRD-positive rates than those in the negative group(P<0.05).ConclusionsGene rearrangement is common in B-ALL species,and gene mutations and co-mutations are common in T-ALL.Patients with E2A-PBX1 gene mutations and JAK/STAT pathway mutations may have a poor prognosis,and they need to expand the sample size and follow up further.Part 2 Significance of JAK3 mutation in adult acute lymphoblastic leukemiaObjectiveThe characteristics of JAK3 gene mutations and co-mutations in adult acute lymphoblastic leukemia(ALL)were analyzed,and the prognostic characteristics of JAK3 gene mutations were attempted to be explored by micro residual disease detection(MRD)and its co-mutated genes.MethodsA retrospective analysis of 246 newly treated adult patients with acute lymphoblastic leukemia diagnosed in our hospital from January 2017 to December 2019,combined with flow cytometry,real-time fluorescence quantitative PCR(RT-PCR),and next-generation sequencing technology((NGS)to detect patients’MRD and 16 mutant genes.SPSS 21.0 was used to analyze the statistical data,the count data was used the χ 2 test,and the measurement data was used to the t-test.P<0.05 indicated that the difference was statistically significant.ResultsOf the 246 ALL patients,JAK3 gene mutations were found in 10 patients,8 were T-ALL,1 B-ALL,and 1 bi-phenic patient,90%of whom had co-mutation of the gene,mostly with NOTCH1.(4 cases),PHF6(3 cases),and FBXW7(2 cases)had co-mutations.A total of 4 JAK3 mutation sites were detected:A573V,R657Q,V674A,and M511I,of which R657Q was the most mutated site(50%),followed by M511I(30%).In addition,one patient had both A573V and R657Q site mutations.In T-ALL,patients with JAK3 mutations were younger than the negative group and had higher platelet counts,but the MRD-positive rate was higher in induction therapy(P<0.05).ConclusionPatients with JAK3 mutations may have a poor prognosis,but they need to expand their sample size and continue follow-up.