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

作　　者：贾西 姚韵倩 廖娜莹 李环[1] 刘慧[1] 余国攀[1] 刘启发[1] 张钰[1] 史鹏程[1] JIA Xi;YAO Yunqian;LIAO Naying;LI Huan;LIU Hui;YU Guopan;LIU Qifa;ZHANG Yu;SHI Pengcheng(Department of Hematology,Nanfang Hospital,Southern Medical University,Guangzhou,510515,China)

机构地区：[1]南方医科大学南方医院血液科,广州510515

出　　处：《临床血液学杂志》2024年第5期318-325,共8页Journal of Clinical Hematology

基　　金：国家自然科学基金(No:82370152);广东省自然科学基金(No:2020A1515010406)。

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,KIT D816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。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).For t(8;21)AML patients,KIT D816 was an independent risk factor for overall survival(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 allogeneic hematopoietic stem cell transplantation was the independent protective factor for cumulative incidence of relapse(P=0.037)and event-free survival(P=0.015).Conclusion t(8;21)and inv(16)/t(16;16)AML are heterogeneous 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 

分 类 号：R733.71[医药卫生—肿瘤]