Association between DNMT3A Mutations and Prognosis of Adults with De Novo Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

Background: DNA methyltransferase 3A (DNMT3A) mutations were considered to be independently associated with unfavorable prognosis in adults with de novo acute myeloid leukemia (AML), however, there are still debates on this topic. Here, we aim to further investigate the association between DNMT3A mutations and prognosis of patients with AML. Methods: Eligible studies were identified from several data bases including PubMed, Embase, Web of Science, ClinicalTrials and the Cochrane Library (up to June 2013). The primary endpoint was overall survival (OS), while relapse-free survival (RFS) and event-free survival (EFS) were chosen as secondary endpoints. If possible, we would pool estimate effects (hazard ratio [HR] with 95% confidence interval[CI]) of outcomes in random and fixed effects models respectively. Results: That twelve cohort studies with 6377 patients exploring the potential significance of DNMT3A mutations on prognosis were included. Patients with DNMT3A mutations had slightly shorter OS (HR = 1.60; 95% CI, 1.31-1.95; P < 0.001), as compared to wild-type carriers. Among the patients younger than 60 years of age, DNMT3A mutations predicted a worse OS (HR = 1.84; 95% CI, 1.36-2.50; P < 0.001). In addition, mutant DNMT3A predicted inferior OS (HR = 2.30; 95% CI, 1.78-2.97; P = 0.862) in patients with unfavorable genotype abnormalities. Similar results were also found in some other subgroups. However, no significant prognostic value was found on OS (HR = 1.40; 95% CI, 0.98-1.99; P = 0.798) in the favorable genotype subgroup. Similar results were found on RFS and EFS under different conditions. Conclusions: DNMT3A mutations have slightly but significantly poor prognostic impact on OS, RFS and EFS of adults with de novo AML in total population and some specific subgroups.