Clinical Characteristic And Prognostic Study Of De Novo Adult Acute Myeloid Leukemia Patients With ASXL1 Mutations

Objectives: To explore the clinical characteristics of de novo adult acute myeloid leukemia(AML) with ASXL1 mutations, as well as the correlation of ASXL1 mutations with some other common AML prognosis related mutations and the prognostic impact of ASXL1 mutations on patients with AML.Methods:A total of 156 de novo adult AML patients who were diagnosed by Morphology, Immunology, Cytogenetics and Molecular Biology(MICM) schema from Fujian Medical University Union Hospital between January, 2013 and August, 2015 were enrolled in this study. Polymerase chain reaction(PCR)and sanger sequencing were used to detect gene mutations.Retrospective analysis was used to assess the clinical characteristics of the included AML patients. Chi-square test and some other statistical methods were used to analyze the association between ASXL1 mutations and some other common mutations, as well as the impact of ASXL1 mutations on de novo adult AML patients.Results:1. Among the included 156 AML patients, 22 cases were detected with ASXL1 mutations(exon12). Of the 22 ASXL1 mutations, 18 cases(81.81%) were identified with missense mutations, 2 cases(9.09%) deletion mutations, 1 case(4.54%) frameshift mutations, and 1 case nonsense mutations.2. When compared AML patients with ASXL1 mutations to those without, we found that there existed no statistical significance in gender distribution, age, initial WBC count, HGB count, PLT lever, LDH, UA, ?-HBDH, percentage of blasts in peripheral blood and bone marrow blast percentage.3. ASXL1 mutations were highest frequently(68.2%) found in M5 subtype according to FAB-classification. Also, ASXL1 mutations were most frequently found in intermediate risk karyotype according to cytogenetic risk categories. Besides, ASXL1 mutations were correlation with TET2 mutations(p<0.001), DNMT3 A mutations(P=0.001) and PHF6 utations(P=0.037).4. When analyzing prognosis, there existed no statistical significance on CR rate and the recurrence rate between AML patients with ASXL1 mutations and those without.5. In 145 patients included in Kaplan-Meier survival analysis, ASXL1 mutations had no impact on OS and EFS. In the exploratory subgroup analysis for AML patient with CN-AML and older(?60 years) AML patients, ASXL1 mutations predicated adverse impact on OS(P=0.016; p=0.011, respectively) and showed adversely prognostic tendency to EFS(p=0.165; p=0.096, respectively).6. We found ASXL1 mutations were independent unfavorable prognostic factors for OS of CN-AML and older(?60 years) AML patients in multivariate analysis. Although ASXL1 mutations were not significantly impacted EFS of older(?60 years) AML in univariate analysis, in multivariate analysis, it showed that ASXL1 mutations were unfavorable factors for EFS of older(?60 years) AML patients.7. We also analyzed the correlation of ASXL1 mutation with some other common AML prognosis related mutations and prognostic impact of those mutation coinciding with or without ASXL1 mutation on OS and EFS of AML patients. The result indicated that thought ASXL1 mutations were associated with TET2, DNMT3 A and PHF6 mutations, when coinciding with ASXL1 mutations, the prognosis of AML patients was not significantly impacted.Conclusion:1. In a cohort of 156 patients with AML, ASXL1 mutation was found in 22(14.10%) patients.2. ASXL1 mutations were more frequently present among M5 and CN-AML and predicted shorter OS among CN-AML and older(?60 years) AML patients.3. ASXL1 mutations were associated with TET2, DNMT3 A and PHF6 mutations, but when coinciding with ASXL1 mutations, the prognosis of AML patients was not significantly impacted.4?ASXL1 mutations were one of the indexes for poor prognosis in elder AML.