Relationship Between CEBPA Gene Mutation And Clinical Characteristics And Prognosis Of A Cute Myeloid Leukemia

Background Acute myeloid leukemia（AML）is a malignant disease of hematopoietic cells whose incidence increases with age and has a high mortality rate.With the development of molecular biology detection technology,the study of gene mutations has gradually gained importance in the clinical understanding and prognostic analysis of AML patients.CEBPA is a basic leucine zipper transcription factor that directs granulocyte differentiation and plays an important role in the transcriptional program driven by hematopoietic stem cell self-renewal and myeloid differentiation.CEBPA gene mutations are common in adult AML patients.The mutations are classified as double mutation and single mutation,and double mutation is associated with clinical features such as young age,high white blood cell count,high hemoglobin count,low platelet count,and a good prognosis.Objective To investigate the mutation rate and occurrence of CEBPA mutations in the AML population,to study the clinical characteristics and prognostic features of AML patients with positive CEBPA mutations,and to provide AML patients with a more in-depth understanding of clinical features and accurate prognostic risk assessment.Methods Clinical data,blood routine,bone marrow cytology,FAB typing;leukemia immunophenotyping,karyotype;13 AML-related genetic mutations detected by generation sequencing,and survival data were collected from 154 AML patients（excluding M3 type）who first visited our hospital on January 1,2018 to December 31,2019,and all patients were diagnosed by MICM method The patients were divided into three groups according to the mode of CEBPA mutation:CEBPA double mutation group（CEBPAdm group）,CEBPA single mutation group（CEBPArm group）,and CEBPA mutation-negative group（CEBPA-group）.Firstly,we compared the age,sex,blood,bone marrow,FAB typing,immunophenotype,and karyotype clinical data between the two groups of CEBPAdm and CEBPA-groups,and secondy,we compared the accompanying genetic mutations in the CEBPAdm,CEBPA-and CEBPArm groups and the prognosis of the three groups.Results A total of 31 cases（20.13%）of the 154 AML patients had CEBPA mutations,including 23（14.94%）in the CEBPAdm group,8（5.19%）in the CEBPAdm group,and 123（79.87%）in the CEBPA-group-the CEBPAdm group was younger than the CEBPAgroup,The mean age of the CEBPAdm group was 41.52±17.42 years.The platelet count was lower（P<0.001）,hemoglobin was higher（P=0.030）,and white blood cell count was higher（P=0.041）in the CEBPAdm group compared to the CEBPA-group,and there were no statistically significant differences in gender distribution,bone marrow primitive cell count between the 2 groups.2.The CEBPAdm group showed more M2 subtype（P=0.001）and less M5 subtype（P=0.016）than the CEBPA-group,and the CEBPAdm group showed more normal karyotype（P=0.001）than the CEBPA-group.3.The CEBPAdm group expressed more CD7 compared with the CEBPA-group（P<0.001）:and the remaining immunophenotypes CD13,CD15,CD33,CD38,CD117,HLA-DR,and CD56 were not statistically signi ficant in the distribution of the 2 groups.4.The CR rate was significantly higher in the CEBPAdm group than in the CEBPAsm and CEBPA-groups（both P<0.05）.OS（26 months,95%CI 16.614 to 35.386 months）and PFS（23 months,95%CI 18.998 to 27.002 months）were significantly prolonged in the CEBPAdm group compared with the remaining two groups（both P<0.05）,while the CEBPAsm did not have this advantage in prognosis,and the difference was not statistically significant compared with the CEBPA-group.5.Atotal of 101（65.58%）of the 154 patients with primary AML had gene mutations.In the comparison of CEBPAdm,CEBPA-,and CEBPAsm groups,CEBPAdm was more combined with WT1 gene mutation（P=0.033）:and the differences in the distribution of NPM1 and FLT3 gene mutations were not statistically significant in the three groups.No statistically significant differences in CR rates and OS and PFS were seen in the comparison between the WT1-CEBPAdm group and the WT1-CEBPAdm group（all P>0.05）.Among the remaining 12 mutations except for CEBPA mutation FLT3 mutation and IDH mutation were associated with OS（P=0.006 P=0.025）,and the remaining 10 gene mutations were not seen to be associated with OS（all P>0.05）.（possibly related to the small number of cases collected in this study）.Conclusion 1.CEBPAdm AML patients with young age at first diagnosis,low platelet count,high hemoglobin and high leukocyte count have high prognostic CR rate,significantly prolonged OS and PFS,good treatment effect,and good prognosis,while CEBPAsm AML patients do not have this prognostic advantage.2.CEBPAdm AML patient’s FAB typing is mostly M2 type,with normal karyotype and mostly expressing CD7 immunophenotype.3.CEBPAdm is mostly combined with WT1 gene mutation,which has no efficacy and prognosis impact on CEBPAdm AML patients.