儿童急性髓系白血病基因突变、染色体核型及融合基因与预后关联分析

Association analysis of gene mutation, chromosome karyotype and fusion gene with prognosis of acute myeloid leukemia in children

摘要

目的 分析儿童急性髓系白血病(AML)基因突变、染色体核型及融合基因与预后的关联性。方法 选择2015年12月至2022年12月徐州医科大学附属医院儿科收治的92例初发AML患儿为研究对象,通过二代测序检测基因突变、染色体R带分析核型、RT-PCR法检测融合基因.生存分析采用Kaplan-Meier法,各组生存之间的比较采用log-rank检验;独立预后因素的评估采用Cox比例风险模型。结果 92例患儿随访中位时间37(1~87)个月,3年总生存率(OS)、无事件生存率(EFS)分别为(74.4±4.9)%、(58.4±5.4)%.单因素分析结果表明C-KIT突变、FLT3-ITD突变及TLS-ERG融合基因阳性是降低OS的因素(χ²值分别为9.039、4.376、4.279,P<0.05);C-KIT突变是降低EFS的因素(χ²=19.626,P<0.05);Cox回归分析结果显示C-KIT突变是影响AML患儿OS及EFS的危险因素,其HR(95%CI)值分别为3.508(1.514~8.129)、3.342(1.744~6.403),P<0.05。结论 C-KIT突变是影响AML患儿预后的独立危险因素.

Abstract

Objective To analyze the association between gene mutations, chromosomal karyotypes, and fusion genes with prognosis in children with acute myeloid leukemia (AML). Methods A total of 92 newly diagnosed pediatric AML patients admitted to the Pediatric Department of the Affiliated Hospital of Xuzhou Medical University from December 2015 to December 2022 were enrolled. Gene mutations were detected using next-generation sequencing (NGS), chromosomal karyotypes were analyzed by R-banding, and fusion genes were identified using RT-PCR. Kaplan-Meier method was used for survival analysis, and comparisons between groups were performed using the log-rank test. Independent prognostic factors were assessed using the Cox proportional hazards model. Results The median follow-up time for the 92 patients was 37 months (range: 1-87 months). The 3-year overall survival (OS) and event-free survival (EFS) rates were (74.4±4.9)% and (58.4±5.4)%, respectively. Univariate analysis showed that C-KIT mutation, FLT3-ITD mutation, and TLS-ERG fusion gene positivity were associated with decreased OS (χ²=9.039, 4.376 and 4.279, respectively, P<0.05), while C-KIT mutation was also associated with reduced EFS (χ²=19.626, P<0.05). Cox regression analysis revealed that C-KIT mutation was an independent adverse prognostic factor for both OS and EFS in pediatric AML, with HR (95%CI) values of 3.508 (1.514-8.129) and 3.342 (1.744-6.403), respectively (P<0.05). Conclusion C-KIT mutations are an independent risk factor for the outcome of children with AML.

关键词

急性髓系白血病 / 基因突变 / 染色体核型 / 融合基因 / 儿童 / 生存率

Key words

acute myeloid leukemia / gene mutation / chromosome karyotype / fusion gene / child / survival rate

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