Mutation And Its Clinical Significance Of Acute Myeloid Leukemia In Elderly Patients

Purpose:Acute myeloid leukemia(AML)is a common type of acute leukemia in the elderly.However,elderly patients with poor chemotherapy tolerance,poor treatment,combined with underlying diseases affect its efficacy and long-term survival.This study aimed to investigate the frequency and prognostic relevance of some leukemia-associated gene mutation in older patients with acute myeloid leukemia.Methods:Next-generation sequencing(NGS)was applied to assess 21 genes in 111older patients(>60 years old)with newly diagnostic AML,including TET2,DNMT3A,NPM1,CEBPα,EZH2,JAK2,U2AF1,RUNX1,NRAS,TP53,IDH2,C-KIT,SRSF2,SF3B1,ASXL1,FLT3-ITD,ETV6,PHF6,CBL,SETBP1,ZRSR2.All patients received the first course of decitabine and reduced dosage of CAG induction(DCAG).Collection of clinical data analyzed the incidence of mutations and their clinical significance.Results:The median age of patients was 67 years.The male to female ration was1.4:1.The most common types of AML were AML with myelodysplasia-related changes and AML-NOS.The total gene mutation rate of geriatric AML patients is as high as 99.1%(110/111).NRAS mutation tended to occur in patients younger than 70years(P=0.03).DNMT3A(P=0.037),RUNX1(P=0.014),TP53(P<0.001)and FLT3-ITD(P=0.002)mutations were different among the four types of leukemias.NPM1(P=0.005)and FLT3-ITD(P=0.014)mutations appear in patients with more than 100×10~9 leukocytes.TP53 mutation was highly correlated with high-risk chromosome karyotypes(P<0.001).Analysis of DCAG reaction,the CR rate in CEBPα-positive patients was higher than those negative patients(P=0.029).NPM1mutation was more likely to occur in the intermediate-risk chromosome group(P=0.004)and were associated with longer DFS(P=0.037)as well as lower recurrence rates(P=0.047).The mutations of TP53,ETV6,FLT3-ITD,poor-risk chromosome type,number of comorbidities above 1,number of gene mutations between 5 and 7were associated with shorter OS and DFS.However,the mutation of SRSF2 was associated with longer OS and DFS.Complete induction of DCAG for the first time was associated with longer OS(all P<0.05).In multivariate analysis,the ETV6mutation,SRSF2 mutation and DCAG induced complete remission for the first time were independent risk factors.The mutation of NPM1 retained independent prognostic significance in DFS(P<0.05).After all,the ETV6 mutation,SRSF2mutation,DCAG induced complete remission for the first time,the NPM1 mutation can be used to predict the prognosis of elderly AML.Conclusion:The genetic mutation rate of elderly AML patient population is high,and its molecular and cytogenetic abnormalities are of great significance for clinical diagnosis and treatment.Introduction: In acute myeloid leukemia(AML),it has been found that harnessing the autophagy process has led to leukemia cell death and had synergistic effects with chemotherapy.BECLIN1 and ATG5 are vital upstream regulators in the macroautophagy signaling pathway.Therefore,we explored the expression levels of BECLIN1 and ATG5 in AML patients and investigated their prognostic value,that of other clinical features.Methods: Real-time quantitative PCR was used to investigate the m RNA levels of BECLIN1 and ATG5 in 101 newly diagnosed leukemia patients.Results: AML samples with CEBPα or C-KIT mutations showed lower BECLIN1 expression levels compared with those without mutations(P=0.044 and P=0.036)and those with the C-KIT mutation showed lower ATG5 expression(P=0.040).Overexpression of BECLIN1 and ATG5 was related to a shorter overall survival(OS;P=0.02 and P=0.035)but not to disease-freesurvival(DFS).In multivariate analysis,the clinical characteristics exhibited no statistically significant differences in OS,except for the FLT3-ITD mutation(P=0.001)and age of the patients(P=0.032).Conclusion: Our results indicate that high levels of BECLIN1 and ATG5 are associated with poor disease outcome.However,they are not independent risk factors for AML and further studies are needed to verify the underlying mechanism.