Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients

• Main Authors: Xiao-Qing Yuan, Peng Chen, Yin-Xiao Du, Ke-Wei Zhu, Dao-Yu Zhang, Han Yan, Han Liu, Yan-Ling Liu, Shan Cao, Gan Zhou, Hui Zeng, Shu-Ping Chen, Xie-Lan Zhao, Jing Yang, Wen-Jing Zeng, Xiao-Ping Chen
• Format: Article
• Language: English
• Published: BMC 2019-07-01
• Series: Journal of Translational Medicine
• Subjects: Acute myeloid leukemia; DNMT3A; R882 mutations; Allele ratio; Prognosis; Aclarubicin
• Online Access: http://link.springer.com/article/10.1186/s12967-019-1959-3

Abstract Background The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. Methods DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed. Results DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10−4 and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035). Conclusion Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.