Pb1759 dnmt3a mutation is not related with unfavorable clinical outcome in acute myeloid leukemia patients

Background: Mutation in DNMT3A (DNA methyltransferase 3A) has been identified as a key factor in the development of hematological malignancy. While some previous reports have suggested that DNMT3A mutation is related with negative outcome in acute myeloid leukemia (AML) patients, the clinical implication and prognostic significance of DNMT3A mutation in AML is still debated. Aims: We intended to investigate the incidence of DNMT3A gene mutation and its association with clinical and laboratory findings and prognosis in Korean AML patients. Methods: From 2012 to 2018, we enrolled forty‐nine patients diagnosed with AML without recurrent genetic abnormalities. We performed Sanger sequencing to analyze DNMT3A mutation using residual bone marrow samples. We also collected other laboratory data and clinical information via electronic medical records. Results: We found DNMT3A mutations in 6 out of 49 AML patients (12.2%). Five patients had the R882H mutation, and one patient the R882C mutation. There was no significant difference in age, complete blood cell count (CBC) parameters, or bone marrow (BM) blast % between the groups with and without DNMT3A mutations. The portion of patients older than 60 years was smaller in DNMT3A mutation positive group (33.3% vs. 60.5%, p = 0.381). DNMT3A mutation group showed higher rate of complete remission (CR) (50% vs. 27.9%, p = 0.353), shorter period to CR (1.1 (CI 1.1 – 1.2) months vs. 1.2 (CI 1.0 – 2.8) months, p = 0.613), and lower relapse rate after CR (0% vs. 41.7%, p = 0.505) than DNMT3A mutation negative group although the difference was not statistically significant. In the survival analysis, the median overall survivals (OS) were 29.0 (CI 5.5 – 52.4) months for DNMT3A mutation positive group and 10.8 (CI 0.5 – 21.0) months for DNMT3A mutation negative group. The median progression free survivals (PFS) were 29.0 months (CI 5.5 – 52.5 months) for DNMT3A mutation positive group and 8.0 months (CI 0.0 – 16.3 months) for DNMT3A mutation negative group. However, the effect of DNMT3A mutation on OS and PFS was not statistically significant ( p = 0.814 and p = 0.528, respectively). In a multivariate analysis, the only independent predictive factors for survival were age (HR: 1.027, p = 0.001) and BM blast % (HR: 1.017, p = 0.016). DNMT3A mutation, sex, and CBC parameters were not independent predictors of survival. Figure 1. Kaplan‐Meier overall survival analysis (A) and progression‐free survival analysis (B) comparing between the groups with and without DNMT3A mutation. Summary/Conclusion: The incidence of DNMT3A mutation was 12.2% in Korean AML patients. DNMT3A mutation tended to be related with favorable outcome although statistically insignificant. This statistical insignificance might be due to the small sample size. Considering all, our results at least provide support for the view that DNMT3A mutations is not an unfavorable prognostic factor in AML patients. image