NPM1 High Mutant Allele Burden is an Adverse Prognostic Factor for AML Patients with Mutated NPM1.
10.19746/j.cnki.issn.1009-2137.2019.02.009
- Author:
Jiang-Xue HOU
1
;
Shu-Juan WANG
1
;
Yan-Fang LIU
2
;
Qian-Qian HAO
1
;
Chong WANG
1
;
Tao LI
1
;
Jun-Jun BAI
1
;
Lin-Xiao LIAO
1
;
Cheng-Yu GUO
1
;
Yin-Yin CHANG
3
;
Meng WANG
1
;
Hui SUN
1
;
Xin-Sheng XIE
1
;
Zhong-Xing JIANG
1
Author Information
1. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
2. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China,E-mail：fccliuyf1@zzu.edu.cn.
3. Shanghai Yuan Qi Biological Medicine Technology Co., Ltd, Shanghai 201400, China.
- Publication Type:Journal Article
- MeSH:
Alleles;
Humans;
Leukemia, Myeloid, Acute;
genetics;
Mutation;
Nuclear Proteins;
genetics;
Prognosis;
fms-Like Tyrosine Kinase 3
- From:
Journal of Experimental Hematology
2019;27(2):365-372
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the clinical features, accompanying gene mutation characteristics and prognostic factors of adult patients with acute myeloid leukemia with mutated NPM1 (NPM1AML).
METHODS:Seventy-three patients with newly diagnosed adult NPM1AML were selected. The mutations of 22 genes were detected by second generation sequencing and 43 fusion genes of AML were detected by real-time fluorescent quantitative PCR. The Kaplan-Meier survival curve and Cox multivariate regression analysis were used to study the prognostic factors.
RESULTS:A total of 74 NPM1 site mutations were detected in 73 patients with NPM1AML. The incidence rates were 92.0% L287fs, 2.7% Q289fs and W288fs, 1.4% L258fs and Q289H, among which 1 patient had 2 NPM1 mutations; the different mutation sites had no effect on the prognosis of NPM1AML. The median value of NPM1 variant allele frequency (VAF) was 35.4% (1.8%-56.6%). Based on the uppermost quartile of 38.4%, the patients were classified as NPM1 VAF>38.4% (NPM1AML) and NPM1 VAF≤38.4% (NPM1AML). Compared with NPM1AML, the early mortality rate was statistically significantly higher (33.3% vs 7.3%, P<0.05), and median EFS (148 d，95%CI 58-238 d vs 372 d，95%CI 264-480 d) (P<0.01) and median OS (179 d 95%CI 6-352 d vs 444 d) (P<0.01) were significantly shorter in NPM1 AML. A total of 126 accompanying gene mutation sites were detected in 87.7% of patients with NPM1AML. The patients with NRAS gene mutation displayed a higher rate of complete remission (100% vs 58%) (P<0.05) and longer median OS (not reached to 320 d, 95%CI 150-490 d) (P<0.05). The 43 fusion genes were examined in 65 out of 73 cases of NPM1AML, and in all the patients the fusion gene test was negative. Multivariate analysis showed that NPM1 VAF>38.4% was an independent prognostic factor for EFS (HR=3.1, 95% CI 1.6-6.4, P<0.01) and OS (HR=3.0, 95% CI 1.4-6.2, P<0.01).
CONCLUSION:The NPM1 gene mutation in AML patients often is accompanied by other gene mutations, while the coexistence of fusion genes is rare; high NPM1 mutant allele burden is an independent prognostic factor for adult AML patients with mutated NPM1.
