{"title":"[基于多基因测序的CEBPA-bZIP突变细胞遗传学正常急性髓系白血病的基因突变谱和风险分层]。","authors":"Lei-Ming Cao, 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","doi":"10.19746/j.cnki.issn.1009-2137.2024.06.001","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with <i>CEBPA-bZIP</i> mutation.</p><p><strong>Methods: </strong>Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with <i>CEBPA-bZIP</i> 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.</p><p><strong>Results: </strong>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<sup>9</sup>/L)+1.406 5×<i>CSF3R</i> mutation positive+2.648 9× <i>KMT2A</i> 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, <i>n</i>=46) and high-risk group (score>0, <i>n</i>=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 <i>P</i> < 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.</p><p><strong>Conclusion: </strong>Adult CN-AML with <i>CEBPA-bZIP</i> mutation has a complex co-mutation pattern. The nomogram model based on mutations of <i>CFS3R, KMT2A</i> 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 <i>CEBPA-bZIP</i> mutation.</p>","PeriodicalId":35777,"journal":{"name":"中国实验血液学杂志","volume":"32 6","pages":"1631-1637"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Genetic Mutation Profile and Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia with <i><i>CEBPA-bZIP</i></i> Mutations Based on Multi-Gene Sequencing].\",\"authors\":\"Lei-Ming Cao, 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\",\"doi\":\"10.19746/j.cnki.issn.1009-2137.2024.06.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To evaluate the gene mutation profile and prognostic significance of adult cytogenetically normal acute myeloid leukemia (CN-AML) with <i>CEBPA-bZIP</i> mutation.</p><p><strong>Methods: </strong>Targeted sequencing was implemented on the diagnostic bone marrow DNA samples of 141 adult CN-AML subjects with <i>CEBPA-bZIP</i> 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.</p><p><strong>Results: </strong>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<sup>9</sup>/L)+1.406 5×<i>CSF3R</i> mutation positive+2.648 9× <i>KMT2A</i> 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, <i>n</i>=46) and high-risk group (score>0, <i>n</i>=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 <i>P</i> < 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.</p><p><strong>Conclusion: </strong>Adult CN-AML with <i>CEBPA-bZIP</i> mutation has a complex co-mutation pattern. The nomogram model based on mutations of <i>CFS3R, KMT2A</i> 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 <i>CEBPA-bZIP</i> mutation.</p>\",\"PeriodicalId\":35777,\"journal\":{\"name\":\"中国实验血液学杂志\",\"volume\":\"32 6\",\"pages\":\"1631-1637\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"中国实验血液学杂志\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.06.001\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"中国实验血液学杂志","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.19746/j.cnki.issn.1009-2137.2024.06.001","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Medicine","Score":null,"Total":0}
[Genetic Mutation Profile and Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia with CEBPA-bZIP Mutations Based on Multi-Gene Sequencing].
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=1.300 2×white blood cell (WBC) (≥18.77×109/L)+1.406 5×CSF3R mutation positive+2.648 9× KMT2A 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, 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.
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