成人核心结合因子相关急性髓系白血病遗传异质性及预后因素分析
Genetic heterogeneity in core-binding factor acute myeloid leukemia and its clinical implication
贾西 1姚韵倩 1廖娜莹 1李环 1刘慧 1余国攀 1刘启发 1张钰 1史鹏程1
作者信息
- 1. 南方医科大学南方医院血液科(广州,510515)
- 折叠
摘要
目的:探讨成人核心结合因子急性髓系白血病(core-binding factor acute myeloid leukemia,CBF-AML)的遗传异质性及预后因素.方法:回顾性分析271例成人新诊断CBF-AML患者的临床资料,包括188例t(8;21)AML患者和83例inv(16)/t(16;16)AML患者.比较2组患者间分子遗传学差异,采用log-rank检验和Cox回归模型分析影响患者生存和复发的因素.结果:t(8;21)AML患者性染色体缺失(33.6％vs 1.5％,P＜0.001)、CD19(58.9％vs 6.8％,P＜0.001)和 CD56 表达(63.8％vs 1.7％,P＜0.001)明显高于 inv(16)/t(16;16)AML 患者.+22 在 inv(16)/t(16;16)AML 患者中明显高于 t(8;21)AML 患者(13.6％vs 0.7％,P＜0.001).KIT 突变(51.8％vs 28.3％,P=0.010)、EZH2 突变(18.8％vs 4.3％,P=0.022)在 t(8;21)AML 患者中的发生率明显高于 inv(16)/t(16;16)AML 患者.FLT3 突变(34.8％vs 12.9％,P=0.003)和WT1 突变(15.2％vs 4.7％,P=0.044)在 inv(16)/t(16;16)AML 患者中的发生率明显高于 t(8;21)AML 患者.对于t(8;21)AML患者,KITD816突变是影响总生存的独立危险因素(P=0.050),而异基因造血干细胞移植是影响总生存的独立保护因素(P=0.029).初诊时骨髓高原始细胞数(P=0.043)、CD19不表达(P=0.008)是影响无事件生存的独立危险因素.KIT D816突变(P=0.014)、CD19不表达(P=0.036)是影响累计复发率的独立危险因素.对于inv(16)/t(16;16)AML患者,髓外浸润是影响无事件生存的独立危险因素(P=0.023),异基因造血干细胞移植是影响累计复发率(P=0.037)和无事件生存(P=0.015)的独立保护因素.结论:成人t(8;21)和inv(16)/t(16;16)AML患者具有显著的遗传学异质性.
Abstract
Objective:To explore the genetic heterogeneity and prognostic factors in adult core-binding factor acute myeloid leukemia(CBF-AML).Methods:The clinical data of 271 newly diagnosed adult CBF-AML were retrospectively analyzed,including 188 patients with t(8;21)AML and 83 patients with inv(16)/t(16;16)AML.Chi-square test was used to compare the difference of molecular genetic between t(8;21)AML and inv(16)/t(16;16)AML.Log-rank test and Cox regression model were used to analyze the impact of clinical factors and gene mutations on survival and relapse in CBF-AML.Results:Sex chromosome deletion,CD19 expression,and CD56 expression were more common in t(8;21)AML(33.6％vs 1.5％,P＜0.001;58.9％vs 6.8％,P＜0.001;63.8％vs 1.7％,P＜0.001),while trisomy 22 was more common in inv(16)/t(16;16)AML(13.6％vs 0.7％,P＜0.001).The incidences of KIT and EZH2 mutations in t(8;21)AML were significantly higher than those in inv(16)/t(16;16)AML(51.8％vs 28.3％,P=0.010;18.8％vs 4.3％,P=0.022).The incidences of FLT3 and WT1 mutations were significantly higher in inv(16)/t(16;16)AML than those in t(8;21)AML(34.8％vs 12.9％,P=0.003;15.2％vs 4.7％,P=0.044).Fort(8;21)AML patients,KIT D816 was an independent risk factor for overall survivai(P=0.050)and allogeneic hematopoietic stem cell transplantation was an independent protective factor for overall survival(P=0.029).Higher bone marrow blasts and CD19 negative were independent risk factors for event-free survival(P=0.043;P=0.008).KIT D816 and CD19 negative were independent risk factors for cumulative incidence of relapse(P=0.014;P=0.036).For inv(16)/t(16;6)AML patients,extramedullary involvement was the independent risk factor for event-free survival(P=0.023)and allo-geneic hematopoietic stem cell transplantation was the independent protective factor for cumulative incidence of re-lapse(P=0.037)and event-free survival(P=0.015).Conclusion:t(8;21)and inv(16)/t(16;16)AML are het-erogeneous in clinical characteristics,cytogenetics,gene mutation profile,and prognostic factors.
关键词
成人核心结合因子相关急性髓系白血病/t(8/21)/inv(16)/t(16/16)/异质性Key words
core-binding factor acute myeloid leukemia/t(8/21)/inv(16)/t(16/16)/heterogeneity引用本文复制引用
基金项目
国家自然科学基金(82370152)
广东省自然科学基金(2020A1515010406)
出版年
2024
NETL
NSTL
万方数据