Gene Mutation in Acute Lymphoblastic Leukemia by DNA Sequencing / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation in adult ALL and its clinical significance.@*METHODS@#Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed.@*RESULTS@#In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ@*CONCLUSION@#There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.

NPM1 High Mutant Allele Burden is an Adverse Prognostic Factor for AML Patients with Mutated NPM1 / 中国实验血液学杂志

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%, P38.4% 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.