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Chinese Journal of Clinicians(Electronic Edition) ›› 2020, Vol. 14 ›› Issue (04): 261-266. doi: 10.3877/cma.j.issn.1674-0785.2020.04.005

Special Issue:

• Clinical Researches • Previous Articles     Next Articles

Prognostic value of DNMT3A gene in patients with non-M3 acute myeloid leukemia

Yan Ren1, Jing Xu1, Weixiao Ren1, Hongwei Wang2,()   

  1. 1. Shanxi Medical University, Taiyuan 030001, China
    2. Shanxi Medical University, Taiyuan 030001, China; Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China
  • Received:2019-07-05 Online:2020-04-15 Published:2020-04-15
  • Contact: Hongwei Wang
  • About author:
    Corresponding author: Wang Hongwei, Email:

Abstract:

Objective

To further clarify the significance of DNMT3A gene mutations in the prognosis of acute myeloid leukemia (AML) patients and the possible mechanism for its impact on the development of AML by analyzing the clinical and laboratory data of non-M3 AML patients.

Methods

R language software was used to download the clinical and mutation data of non-M3 AML patients from The Cancer Genome Atlas (TCGA). The patients were divided into groups according to the mutation status, and the differences of peripheral blood leukocyte count (WBC), proportion of bone marrow primordial cells, event free survival, and overall survival (OS) were compared. The patients were also divided into groups according to their age and survival curves were plotted using the Kaplan-Meier method. The log-rank test was used to compare the survival rate between patients younger than 60 years old and those older than 60 years old, as well as between the DNMT3A mutation group and the wild type group. Cox proportional risk model was used to conduct single- and multiple-factor analyses of the impact of factors such as DNMT3A mutation, its accompanying mutation, and age stratification on the OS of patients.

Results

A total of 180 non-M3 AML patients were included. WBC in the mutation group was significantly higher than that in the wild type group (Z=-2.606, P=0.009), and the mutation of DNMT3A was more common in the middle risk patients. Mutations of DNMT3A often occurred together with FLT3, NPM1, and IDH1 mutations. The event-free survival of the DNMT3Awt/FLT3wt group was significantly longer than that of the DNMT3Amut/FLT3mut group (11.00 months vs 6.15 months, P=0.005), but had no significant difference compared with that of the DNMT3Amut/FLT3wt or DNMT3Awt/FLT3mut group. Cox multivariate analysis showed that advanced age was an independent risk factor for OS of AML patients (P<0.001). DNMT3A R882 mutation was an independent predictor of poor prognosis in AML patients (P=0.009).

Conclusion

Age over 60 years and DNMT3AR882 mutation are independent predictors of poor prognosis. Compared with patients with DNMT3Awt/FLT3wt, DNMT3Amut/FLT3wt, and DNMT3Awt/FLT3mut, patients with DNMT3Amut/FLT3mut have worse clinical consequences.

Key words: Acute myeloid leukemia, DNMT3A mutation, Prognosis

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