Biological and clinical influences of NPM1 in acute myeloid leukemia patients with DNMT3A mutations

• Main Authors: Yang X, Shi J, Zhang X, Zhang G, Zhang J, Yang S, Wang J, Ke X, Fu L
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-08-01
• Series: Cancer Management and Research
• Subjects: AML; DNA methyltransferases 3A; nucleophosmin 1; next generation sequencing; prognosis
• Online Access: https://www.dovepress.com/biological-and-clinical-influences-of-npm1-in-acute-myeloid-leukemia-p-peer-reviewed-article-CMAR

Xinrui Yang,1 Jinlong Shi,2 Xinpei Zhang,1 Gaoqi Zhang,1 Jilei Zhang,1 Siyuan Yang,1 Jing Wang,1 Xiaoyan Ke,1 Lin Fu1 1Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, China; 2Department of Biomedical Engineering, Chinese PLA General Hospital, Beijing 100853, China Purpose: DNMT3A and NPM1 mutations are known to impact the prognosis of acute myeloid leukemia (AML). DNMT3A mutations are negative prognostic factors, while NPM1 mutations are low-risk factors and inclined to concurrently appear with DNMT3A mutations. In this study, we aimed to find out how NPM1 mutations affect patients’ outcomes in the background of DNMT3A mutations. Patients and methods: We screened The Cancer Genome Atlas (TCGA) database and found 51 AML patients with DNMT3A mutations. Of them, 28 patients had a combination of NPM1 mutations. Results: In all, NPM1 had the highest mutation frequency (n=28, 54.9%). DNMT3Amut/NPM1mut patients had higher bone marrow (BM) blasts (P=0.015), higher FLT3-ITD/TKD rate (P=0.004), and lower IDH2 mutation rate (P=0.014) than the DNMT3Amut/NPM1wild patients, while their prognoses were the same as the DNMT3Amut/NPM1wild patients (P>0.1). All 51 patients benefited from hematopoietic stem cell transplantation (HSCT) treatment (P=0.005 and 0.001 for event-free survival [EFS] and overall survival [OS], respectively). In the 23 patients with DNMT3Amut/NPM1wild, those who received HSCT had prolonged EFS and OS (P=0.043 and 0.008, respectively), while HSCT treatment did not produce a positive impact on EFS and OS in the remaining 28 patients with DNMT3Amut/NPM1mut (P=0.056 and 0.053, respectively). Conclusion: Our study found that NPM1 mutations influenced BM blasts’ percentage, FLT3-ITD/TKD rate, and IDH2 mutation rate in AML patients with DNMT3A mutations but made little difference to the overall prognosis. While HSCT treatments benefited all DNMT3Amut patients, it was better for DNMT3Amut/NPM1wild patients to extend their EFS and OS. Keywords: AML, DNA methyltransferases 3A, nucleophosmin 1, next-generation sequencing, prognosis