Genetic Mutation Profile and Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia with CEBPA-bZIP Mutations Based on Multi-Gene Sequencing
10.19746/j.cnki.issn1009-2137.2024.06.001
- VernacularTitle:基于多基因测序研究伴CEBPA-bZIP突变的成人正常核型急性髓系白血病的基因突变谱及危险分层
- Author:
Lei-Ming CAO
1
;
Ming-Yue LIAO
;
Ya-Lan ZHOU
;
Hao JIANG
;
Qian JIANG
;
Ying-Jun CHANG
;
Lan-Ping XU
;
Xiao-Hui ZHANG
;
Xiao-Jun HUANG
;
Guo-Rui RUAN
Author Information
1. 北京大学人民医院
- Keywords:
next-generation sequencing;
acute myeloid leukemia;
normal karyotype;
CEBPA-bZIP mutation;
nomogram model
- From:
Journal of Experimental Hematology
2024;32(6):1631-1637
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with CEBPA-bZIP mutation. Methods:Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with CEBPA-bZIP mutation. The nomogram model for leukemia-free survival (LFS) rate was generated by combining genetic abnormalities and clinical data. Risk stratification was conducted based on prognostic variables and the effect of risk-adjusted consolidation therapy was investigated by Kaplan-Meier method. Results:Four variables were finally included in our nomogram model after multivariate Cox analysis,and an equation for risk score calculation was obtained,risk score=1.3002×white blood cell (WBC) (≥18.77×109/L)+1.4065×CSF3R mutation positive+2.6489×KMT2A mutation positive+1.0128×DNA methylation-related genes mutation positive. According to the nomogram model,patients were further divided into low-risk group (score=0,n=46) and high-risk group (score>0,n=95). Prognostic analysis showed that the 5-year LFS rate,5-year overall survival (OS) rate,and 5-year cumulative incidence of relapse (CIR) of patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the high-risk group were 93.5％,97.1％,and 3.5％,while those in patients who received maintenance chemotherapy were 32.9％,70.5％,and 63.4％,respectively. The differences were statistically significant (all P<0.05). Allo-HSCT could significantly improve the prognosis of patients in high-risk group. However,no corresponding benefit was observed in the low-risk group. Conclusion:Adult CN-AML with CEBPA-bZIP mutation has a complex co-mutation pattern. The nomogram model based on mutations of CFS3R,KMT2A and DNA methylation-related genes together with WBC count can further divide this subset of patients into a relatively low-risk group and a relatively high-risk group. For individuals in the high-risk group,allo-HSCT is proposed as post-remission therapy. The above data will benefit the prognosis estimation and treatment decision for adult CN-AML with CEBPA-bZIP mutation.
