【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。更多还原

【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). 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.更多还原