CCAAT增强子结合蛋白A（CEBPA）是调节血液发育过程中髓系分化和造血干祖细胞活性的关键转录因子之一。CEBPA基因突变常见于急性髓系白血病（AML）中,最近研究表明CEBPA bZIP框内单位点和经典双等位基因突变AML患者均具有类似的临床特征,已被单独划分为AML亚群。CEBPA bZIP框内突变而非传统的双等位CEBPA基因突变成为AML良好预后的分子指标,表明其在AML疾病进展和治疗预后中的重要性和特殊性。本文将从CEBPA蛋白在血液系统中的功能、CEBPA bZIP框内突变AML的临床特征与分子作用机制、以及伴CEBPA突变AML的治疗现状等方面进行综述,为进一步研究CEBPA bZIP框内突变在AML中的致病性和精准治疗新药物开发提供参考。

CCAAT enhancer-binding protein A（CEBPA）is one of the key transcription factors regulating myeloid differentiation and hematopoietic stem/progenitor cell maintenance during hematopoiesis．CEBPA gene mutations are commonly found in acute myeloid leukemia（AML）．Recent studies have demonstrated that AML patients haboring single CEBPA bZIP in-frame mutations or classical bi-allelic CEBPA mutations show similar clinical features and it has been individually classified as AML subgroup．Additionally,it is CEBPA bZIP in-frame mutations rather than the traditional biallelic CEBPA mutations that have emerged as a molecular indicator of favorable prognosis for clinical AML management,suggesting its importance and specificity in AML disease progression and therapeutic prognosis．Here,we reviewed serval aspects including the hematopoietic function of CEBPA protein,the clinical features and molecular mechanisms of AML with CEBPA bZIP in-frame mutations,and the current status of the treatment of AML with CEBPA mutations,which will provide a reference for further study of the pathogenicity of CEBPA bZIP in-frame mutations in AML and the development of new drugs for precision therapy．

目的 随着治疗水平和疗效的不断提高,急性白血病患者的生存质量越来越受到广泛的关注,本研究旨在探讨急性白血病(AML)患者化疗后生活质量及其相关因素。方法 采用癌症患者生存质量测定量表(European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30)中文版、患者一般状况调查问卷,对268例按照AML患者治疗后1年生活质量进行调查,并将EORTC-QLQ-C30各领域评分与患者的特征进行相关性分析。结果 AML患者年龄、FAB分型、是否恢复工作、ECOG评分、婚姻状态、生存质量评分比较上,差异有统计学意义(P>0.05);不同年龄组AML患者PF、RF、EF、SF、QL、FI评分比较上,差异有统计学意义(P<0.05);不同分型AML患者患者RF、EF、SF、QL、DY、SL、FI评分比较上,差异有统计学意义(P<0.05),恢复工作的AML患者PF、RF、SF、QL评分高于未恢复工作的AML患者,恢复工作的AML患者FA、DY、FI评分则低于未恢复工作的AML患者(P<0.05),结婚AML患者PF、RF、SF、QL评分高于未结婚患者,结婚AML患者FA评分低于未结婚患者(P<0.05);逐步多元回归分析发现,年龄、分型、ECOG评分、婚姻状况与AML生存质量有关。结论 高龄、非M3型、ECOG评分高、未婚是AML生存质量差危险因素,可能作为改善AML患者生活质量预期指标。

Objective With the continuous improvement of treatment level and efficacy, the quality of life of patients with acute myeloid leukemia (AML) has attracted more and more extensive attention. This study aimed to explore the quality of life and related factors of patients with acute leukemia (AML) after chemotherapy. Methods The Chinese version of the quality of life scale for cancer patients(European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30, and the general situation questionnaire were was used to investigate quality of life for 268 AML patients one year after treatment.And then the correlation between the EORTC-QLQ-C30 scores in various fields and the characteristics of patients were analyzed. Results There were statistical differences in the scores of age, AML types, work(yes or no),ECOG scores, and marital status in patients (P<0.05).The differences of PF, RF, EF, SF, QL, FI score of AL in different age groups were statistically significant (P<0.05), The PF, RF, EF, SF, QL and FI scores of AML patients in different age groups were statistical different (P<0.05).The scores of PF, RF, SF and QL in AML patients who returned to work were higher than those in AML patients who did not returned to work,while FA, DY and FI scores were the opposite(P<0.05).The PF, RF, SF and QL scores of married AML patients were higher than those of unmarried AML patients,while FA scores were the opposite(P<0.05).Age, classification, ECOG score, marital status were found to be associated with quality of life of AML patients by stepwise multiple regression analysis (P<0.05). Conclusion Old age, non-M3 type, high ECOG score, and unmarried are risk factors for poor quality of life for AML, which may serve as expected indicators for improving the quality of life of patients with acute leukemia.

目的 探讨FLT3及C-kit基因突变在急性髓细胞白血病(AML)中的临床意义。方法 回顾性分析南方医院2010年1月—2013年12月期间初诊AML患者的临床资料,PCR分析FLT3及C-kit基因突变情况。结果 248例初诊AML患者中, FLT3-ITD突变率为16.9%,TKD突变率为3.2%,C-kit8号外显子突变率为1%,17号外显子突变率为5.2%;FLT3-ITD突变更倾向发生于正常染色体核型的AML患者;FLT3突变阳性组及C-kit突变阳性组患者的外周血白细胞数高于基因突变阴性组,染色体核型正常患者的无病生存时间较阴性组缩短(P<0.05)。但是对血红蛋白、血小板及完全缓解率(CR率)并无影响(P>0.05)。结论 FLT3及C-kit突变的AML患者有较差的临床预后。

Objective This study was to investigate the prognostic value of FLT3 and C-kit gene mutations in patients with acute myeloid leukemia (AML). Methods We retrospect and analyzed the data of the 248patients with newly diagnosed AML from January 2013 to December 2010. FLT3 and C-kit gene mutations was detected by Polymerase chain reaction (PCR). Results Among these 248 subjects, the FLT3-ITD mutation rate was 16.9%, FLT3-TKD was 3.2%, C-kit 8 exon mutation rate was 1% and 17exon mutationwas 5.2%. FLT3-ITD mutation likely occurred in AML patients with normal karyotype. The patients with FLT3-ITD mutation or C-kit mutation had significantly higher PWBC and shorter DFS than patients without gene mutations (P< 0.05), but there was no significantly differences in sex, age, Hb, PLT and CR rate of the first course induction chemotherapy among groups (P>0.05). Conclusion Among patients with AML,FLT3-ITD and C-kit mutations were associated with worse prognosis.

    CCAAT增强子结合蛋白A（CEBPA）是调节血液发育过程中髓系分化和造血干祖细胞活性的关键转录因子之一。CEBPA基因突变常见于急性髓系白血病（AML）中，最近研究表明CEBPA bZIP框内单位点和经典双等位基因突变AML患者均具有类似的临床特征，已被单独划分为AML亚群。CEBPA bZIP框内突变而非传统的双等位CEBPA基因突变成为AML良好预后的分子指标，表明其在AML疾病进展和治疗预后中的重要性和特殊性。本文将从CEBPA蛋白在血液系统中的功能、CEBPA bZIP框内突变AML的临床特征与分子作用机制、以及伴CEBPA突变AML的治疗现状等方面进行综述，为进一步研究CEBPA bZIP框内突变在AML中的致病性和精准治疗新药物开发提供参考。

   CAAT enhancer-binding protein A（CEBPA）is one of the  key transcription factors  regulating myeloid differentiation and hematopoietic stem/progenitor cell maintenance during hematopoiesis．CEBPA gene mutations are commonly found in acute myeloid leukemia（AML）．Recent studies have demonstrated that AML patients haboring single CEBPA bZIP in-frame mutations or classical bi-allelic CEBPA mutations show similar clinical features and it has been individually classified as AML subgroup．Additionally，it is CEBPA bZIP in-frame mutations rather than the traditional biallelic CEBPA mutations that have emerged as a molecular indicator of favorable prognosis for clinical AML management，suggesting its importance and specificity in AML disease progression and therapeutic prognosis．Here，we reviewed serval aspects including the hematopoietic function of CEBPA protein，the clinical features and molecular mechanisms of AML with CEBPA bZIP in-frame mutations，and the current status of the treatment of AML with CEBPA mutations，which will provide a reference for further study of the pathogenicity of CEBPA bZIP in-frame mutations in AML and the development of new drugs for precision therapy．