The Influence Of Gene Mutation On The Prognosis Of Core-Binding Factor Acute Myeloid Leukemia

Objective: To investigate the gene mutation pattern of core binding factor associated acute myeloid leukemia(CBF-AML)and its influence on prognosis.Methods: One hundred and four patients with CBF-AML were enrolled,including 86 patients with RUNX1-RUNX1T1 fusion gene positive and 18 patients with CBFB-MYH11 fusion gene positive.High-throughput gene sequencing was used to sequence and analyze the common mutations of 58 blood tumors in 104 patients with CBF-AML.The influence of different gene mutations on the general characteristics,laboratory indicators,and prognosis of patients were analyzed.Result: 1.The median age of 104 patients with CBF-AML was 15(1-68),of which 51(49.04%)were under 14 years old,47(45.19%)were between 15 and 55 years old and 6(5.77%)were over 55 years old.Ninety-three patients underwent karyotype analysis at the time of initial diagnosis.Loss of sex chromosome,which is the most common additional chromosomal abnormality,was found in 39.78%(37/93)of 93 patients and occurred totally in the RUNX1-RUNX1T1 patient group.There was statistically significant difference when compared with the CBFB-MYH11 group(P<0.001).2.Among the 104 patients,96 were positive in gene mutation,which distributed in 24 genes.Mutation rate of KIT was the highest(53.85%),followed by NRAS(17.31%)and ASXL2(13.46%).The mutation rate of RAS gene in CBFB-MYH11 group was significantly higher than that in RUNX1-RUNX1T1 group(NRAS: 50.00% vs 16.28%,P<0.001;KRAS: 22.22% vs 3.48%,P=0.016).The mutations of ASXL2,CSF3 R,JAK1,JAK2,and JAK3 genes were found only in RUNX1-RUNX1T1 group,but there was no statistical difference compared with those in CBFB-MYH11 group.3.In terms of the influence of gene mutation on clinical characteristics of patients,the age of the positive group was younger than that of the negative group(P=0.021);the proportion of bone marrow blast cells in KIT mutation patients was significantly higher than that in KIT mutation negative group(P=0.011)at the time of initial diagnosis;the proportion of bone marrow blast cells in FLT3 mutation patients was significantly higher than that in FLT3 mutation negative group(P=0.037)at the time of initial diagnosis;and the WBC in NRAS mutation patients was significantly higher than that in NRAS mutation negative group(P<0.001)at the time of initial diagnosis.Loss of sex chromosome was correlated with KIT mutation(67.57% vs 44.64%,P=0.035).RAS mutation and loss of sex chromosome were mutually exclusive(NRAS 2.7% vs 26.79%,P=0.002;KRAS 0 vs 12.5%,P=0.039).4.Ninety-six CBF-AML patients were followed up,69 of whom received allogenetic hematopoietic stem cell transplantation(allo-HSCT).FLT3 mutation is a prognosis disadvantage factor for EFS in the whole patients(P=0.022).Patients with KIT mutation who were without allo-HSCT treatment had significantly lower OS and EFS than those without KIT mutation(OS,P=0.0143;EFS,P=0.033),but no adverse effects of KIT mutation on OS and EFS were found in allo-HSCT group.Among 52 KIT mutation positive patients,OS and EFS were worse in patients with concurrent FLT3 mutation(OS,P=0.004;EFS,P=0.01),while OS was worse in patients with concurrent TET2 mutation(P=0.042).Among KIT mutation positive patients,OS in allo-HSCT group was higher than that in non-transplantation group(P=0.014).Conclusion: KIT mutation,which is related to sex chromosome loss,is the most common gene mutation in CBF-AML patients.In patients without allo-HSCT treatment,KIT mutation were a prognostic disadvantage factor in patients,but no influence of KIT mutation on OS and EFS was found in patients with allo-HSCT treatment,suggesting that allo-HSCT treatment should be recommended for patients with positive KIT mutation to improve their prognosis.The prognosis of patients with KIT mutation was worse if FLT3 or TET2 mutation coexisted,therefore early allo-HSCT treatment is recommended.