Cao Lei-Ming, Liao Ming-Yue, Zhou Ya-Lan, Jiang Hao, Jiang Qian, Chang Ying-Jun, Xu Lan-Ping, Zhang Xiao-Hui, Huang Xiao-Jun, Ruan Guo-Rui
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University,Beijing 100044, China.
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100044, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Dec;32(6):1631-1637. doi: 10.19746/j.cnki.issn.1009-2137.2024.06.001.
To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with mutation.
Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with 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.
Four variables were finally included in our nomogram model after multivariate Cox analysis, and an equation for risk score calculation was obtained, risk score=1.300 2×white blood cell (WBC) (≥18.77×10/L)+1.406 5× mutation positive+2.648 9× mutation positive+1.012 8×DNA methylation-related genes mutation positive. According to the nomogram model, patients were further divided into low-risk group (score=0, =46) and high-risk group (score>0, =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 < 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.
Adult CN-AML with mutation has a complex co-mutation pattern. The nomogram model based on mutations of 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 mutation.
评估伴有 突变的成人细胞遗传学正常急性髓系白血病（CN-AML）的基因突变谱及预后意义。
对141例伴有 突变的成人CN-AML患者的诊断性骨髓DNA样本进行靶向测序。通过整合遗传异常和临床数据生成无白血病生存（LFS）率的列线图模型。基于预后变量进行风险分层，并采用Kaplan-Meier法研究风险调整巩固治疗的效果。
多因素Cox分析后，最终有4个变量纳入我们的列线图模型，得到风险评分计算方程，风险评分=1.300 2×白细胞（WBC）（≥18.77×10⁹/L）+1.406 5× 突变阳性+2.648 9× 突变阳性+1.012 8×DNA甲基化相关基因 突变阳性。根据列线图模型，患者进一步分为低风险组（评分=0，n=46）和高风险组（评分>0，n=95）。预后分析显示，高风险组接受异基因造血干细胞移植（allo-HSCT）患者的5年LFS率、5年总生存（OS）率和5年累积复发率（CIR）分别为93.5%、97.1%和3.5%，而接受维持化疗患者的分别为32.9%、70.5%和63.4%。差异有统计学意义（均P<0.05）。allo-HSCT可显著改善高风险组患者预后。然而，低风险组未观察到相应获益。
伴有 突变的成人CN-AML具有复杂的共突变模式。基于 和DNA甲基化相关基因 突变以及WBC计数的列线图模型可将该亚组患者进一步分为相对低风险组和相对高风险组。对于高风险组个体，建议缓解后进行allo-HSCT治疗。上述数据将有助于伴有 突变的成人CN-AML的预后评估和治疗决策。
