Application and clinical study of clonal heterogeneity analysis in acute myeloid leukemia
10.3760/cma.j.issn.0253-2727.2020.06.009
- VernacularTitle:克隆异质性分析在急性髓系白血病中的应用及临床研究
- Author:
Xiaodong LYU
1
;
Zhen GUO
;
Yangwei LI
;
Jieying HU
;
Ruihua FAN
;
Yongping SONG
Author Information
1. 郑州大学附属肿瘤医院、河南省肿瘤医院中心实验室 450008
- Keywords:
Clonal heterogeneity;
Gene mutation;
Leukemia, myeloid, acute;
High-throughput sequencing
- From:
Chinese Journal of Hematology
2020;41(6):483-489
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aimed to explore the characteristics and clinical value of clonal heterogeneity in acute myeloid leukemia (AML) .Method:A high-throughput sequencing was carried out to detect 68 related genes in 465 AML patients. Clonal heterogeneity was analyzed based on variant allele frequency (VAF) and flow cytometry results combined with clinical data.Results:Gene mutations were discovered in 338 (81.4%) newly diagnosed patients, and 2 or more clones were significantly increased in patients with DNMT3A, NRAS, and RUNX1 mutations (DNMT3A, χ2=15.23; P<0.001; NRAS, χ2=19.866; P<0.001; RUNX1, χ2=23.647; P<0.001) . The number of clones significantly differed between groups at different ages ( χ2=17.505, P=0.022) . The proportion of carrying 2 and ≥3 clones increased in patients aged more than 60 years old. There was a significant difference in the clonal heterogeneity between newly diagnosed patients and relapsed or secondary patients ( χ2=11.302, P=0.010) . Moreover, the proportion of patients with clonal heterogeneity gradually increased according to their prognostic risk ( χ2=17.505, P=0.022) . Based on the clone analysis, the proportion of primary clones of patients with RUNX1 mutation was higher ( χ2=4.527, P=0.033) . The analysis of clonal heterogeneity and efficacy demonstrated that patients with three or more clones had significantly lower overall survival (OS) and progression-free survival (PFS) compared to other patients (OS, χ2=13.533; P=0.004; PFS, χ2=9.817; P=0.020) , while in the intermediate-risk group, patients with a significant clonal heterogeneity also exhibited a significant decrease in PFS ( χ2=10.883, P=0.012) . Cox regression multivariate analysis revealed that carrying three or more clones was an independent factor affecting prognosis, and OS and PFS were significantly lower than those of patients without clones (OS, HR=3.296; 95% CI, 1.568-6.932; P=0.002; PFS, HR=3.241; 95% CI, 1.411-7.440; P=0.006) . Conclusion:Clonal heterogeneity may reflect the biological characteristics of a tumor, suggesting its drug resistance, refractory, and invasiveness, and further evaluate the treatment effect and prognosis of patients.
