摘要目的 探讨急性髓系白血病(AML)患者转录因子CCAAT/增强子结合蛋白(CEBPA)基因的突变率、突变特点及临床意义.方法 采用PCR扩增产物片段长度分析及直接测序分析法检测206例初治AML患者CEBPA基因全部编码区突变情况.结果 206例AML患者中31例检测到CEBPA基因突变,突变率为15％,23例为双突变,8例为单突变.CEBPA基因突变常见于M2型或预后中等组患者.与CEBPA野生型组比,CEBPA基因突变患者白细胞计数较高[突变型和野生型患者分别为20.92(0.86 ～ 351.43)×109/L和8.17(0.47～ 295.20)×109/L,P=0.003]、血红蛋白水平较高[97.5(51～ 128) g/L和80.5(13～ 153) g/L,P=0.015],血小板计数较低[27.5(5～81)×109/L和44(3～548)×109/L (P=0.004)].CEBPA基因突变患者的完全缓解率高于野生型患者,差异有统计学意义(P=0.009).与CEBPA双突变患者相比,M5型CEBPA单突变患者更易伴随NPM1突变(0对25％)(P=0.013).动态跟踪20例患者,临床缓解后未再检出CEBPA基因突变,而复发患者则伴有同样的位点突变.PCR片段长度分析与测序分析结果的符合率为100％.结论 CEBPA基因突变是AML患者常见的分子突变类型,CEBPA基因突变患者的临床特征和疾病状态有关,其突变检测可作为AML患者疾病状态的监测指标之一;M5型CEBPA单突变患者更易伴随NPM1突变.

abstractsObjective To investigate the incidence,molecular features and clinical significance of CCAAT/enhancer binding protein alpha (CEBPA) gene mutation in patients with acute myeloid leukemia (AML).Methods Mutation analysis of the entire coding region of CEBPA gene in 206 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis and fragment length analysis.Results Of 206 AML patients,31 (15％) had CEBPA gene mutations,including 23 with double mutations (duCEBPA) and 8 with single mutation (siCEBPA).CEBPA gene mutations presented mainly in M2 subtype or intermediate risk patients.As compared with those with wild type CEBPA gene,patients with mutated CEBPA gene were of higher white blood cell counts [20.92(0.86-351.43) × 109/L vs 8.17(0.47-295.2)× 109/L,P=0.003],higher hemoglobin levels [97.5(51-128) g/L vs 80.5 (13-153) g/L,P=0.015] and lower platelet counts [27.5(5-81)× 109/L vs 44 (3-548)× 109/L,P=0.004].Patients with CEBPA gene mutation had higher complete remission (CR) rate than those with wild type (P=0.009).While co-existing of NPM1 and siCEBPA mutations was observed in M5 subtype (2/8,25％),NPM1 gene mutation was not present in any patients with duCEBPA mutation (0/23,0％).Dynamic tracking analysis showed that CEBPA mutations disappeared at CR,and the same mutations re-appeared at relapse.When compared to sequence analysis,the coincidcncc rate of CEBPA mutations detected by fragment length analysis was 100％ (54/54).Conclusions CEBPA gene mutation is a recurring genetic change in AML patients and has a certain correlation with clinical and laboratory features.It could be reliably used as a potential marker for minimal residual disease follow up.The prognostic significance of co-existing of siCEBPA with NPM1 mutations in patients with AML-M5 subtype needs further investigation.