Prognostic Value Of Cloned Genetic Mutations Detected By Second-generation Sequencing In Core-binding Factor Acute Myeloid Leukemia

Objective:To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with core-binding factor acute myeloid leukemia(CBF-AML)who achieved the first complete remission(CR1)state after 1 to 2 courses of induction chemotherapy.Methods:Retrospectively analyzed the clinical and follow-up data of 190 adult CBFAML patients in CR1 state who were admitted to our center from July 2011 to August 2017.Log-Rank test and Cox regression model were used to figure out the impact of clinical factors and gene mutations for prognosis.Results:Among the 190 CBF-AML patients,134 cases were RUNX1-RUNXIT1 AML,and 56 cases were CBFB-MYH11 AML.The most common was KIT mutation(46.8%),followed by NRAS(20.5%),FLT3(18.4%),ASXL2(14.2%),KRAS(11.0%),ASXL1(9.4%).Sorted by gene function,the most common mutations involved genes affecting tyrosine kinase signaling(7 5.8%),followed by chromatin modifiers(29.5%),transcription factors(9.5%),DNA methylation(8.9%),tumor suppressors(8.4%),RNA splicing factors(2.1%),cohesion complex(1.6%),and others(1.6%).The gene mutation pattern of CBF-AML subtypes was significantly different.Chromatin modification-related gene mutations were only found in the RUNX1-RUNXIT1 group,but they had no significant impact on the prognosis of these patients(P>0.05).According to subgroup analysis,patients receiving intensive consolidation therapy who harbored KIT mutations had shorter DFS(P<0.001),and patients with KIT mutations who received allogeneic hematopoietic stem cell transplantation(allo-HSCT)had longer DFS(P=0.001).Patients with positive mutations in chromatin modification-related genes and receiving allo-HSCT had the best prognosis.Multivariate analysis identified that KIT exon 17 mutation was an independent predictor of inferior OS and DFS in the RUNX1-RUNXIT1 group(P<0.001),and allo-HSCT was an independent predictor of superior DFS in the RUNX1-RUNXIT1 group(P=0.024).Conclusions:The clinical mutatome of CBF-AML subtypes is obviously heterogeneous.RUNX1-RUNXIT1 AML patients with KIT exon 17 mutations may have a poor prognosis.Receiving allo-HSCT therapy may improve the prognosis of these patients.Receiving allo-HSCT therapy may also lead to a better prognosis for patients with positive mutations in chromatin modification-related genes.