中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2013年
7期
566-571
,共6页
韩聪%林冬%艾晓非%王芳%孙海燕%王敏%秘营昌%王建祥%汝昆
韓聰%林鼕%艾曉非%王芳%孫海燕%王敏%祕營昌%王建祥%汝昆
한총%림동%애효비%왕방%손해연%왕민%비영창%왕건상%여곤
白血病,髓样,急性%基因,CEBPA%基因,NPM1%DNA突变
白血病,髓樣,急性%基因,CEBPA%基因,NPM1%DNA突變
백혈병,수양,급성%기인,CEBPA%기인,NPM1%DNA돌변
Leukemia,myeloid,acute%Gene,CEBPA%Gene,NPM1%DNA mutation
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.
目的 探討急性髓繫白血病(AML)患者轉錄因子CCAAT/增彊子結閤蛋白(CEBPA)基因的突變率、突變特點及臨床意義.方法 採用PCR擴增產物片段長度分析及直接測序分析法檢測206例初治AML患者CEBPA基因全部編碼區突變情況.結果 206例AML患者中31例檢測到CEBPA基因突變,突變率為15％,23例為雙突變,8例為單突變.CEBPA基因突變常見于M2型或預後中等組患者.與CEBPA野生型組比,CEBPA基因突變患者白細胞計數較高[突變型和野生型患者分彆為20.92(0.86 ～ 351.43)×109/L和8.17(0.47～ 295.20)×109/L,P=0.003]、血紅蛋白水平較高[97.5(51～ 128) g/L和80.5(13～ 153) g/L,P=0.015],血小闆計數較低[27.5(5～81)×109/L和44(3～548)×109/L (P=0.004)].CEBPA基因突變患者的完全緩解率高于野生型患者,差異有統計學意義(P=0.009).與CEBPA雙突變患者相比,M5型CEBPA單突變患者更易伴隨NPM1突變(0對25％)(P=0.013).動態跟蹤20例患者,臨床緩解後未再檢齣CEBPA基因突變,而複髮患者則伴有同樣的位點突變.PCR片段長度分析與測序分析結果的符閤率為100％.結論 CEBPA基因突變是AML患者常見的分子突變類型,CEBPA基因突變患者的臨床特徵和疾病狀態有關,其突變檢測可作為AML患者疾病狀態的鑑測指標之一;M5型CEBPA單突變患者更易伴隨NPM1突變.
목적 탐토급성수계백혈병(AML)환자전록인자CCAAT/증강자결합단백(CEBPA)기인적돌변솔、돌변특점급림상의의.방법 채용PCR확증산물편단장도분석급직접측서분석법검측206례초치AML환자CEBPA기인전부편마구돌변정황.결과 206례AML환자중31례검측도CEBPA기인돌변,돌변솔위15％,23례위쌍돌변,8례위단돌변.CEBPA기인돌변상견우M2형혹예후중등조환자.여CEBPA야생형조비,CEBPA기인돌변환자백세포계수교고[돌변형화야생형환자분별위20.92(0.86 ～ 351.43)×109/L화8.17(0.47～ 295.20)×109/L,P=0.003]、혈홍단백수평교고[97.5(51～ 128) g/L화80.5(13～ 153) g/L,P=0.015],혈소판계수교저[27.5(5～81)×109/L화44(3～548)×109/L (P=0.004)].CEBPA기인돌변환자적완전완해솔고우야생형환자,차이유통계학의의(P=0.009).여CEBPA쌍돌변환자상비,M5형CEBPA단돌변환자경역반수NPM1돌변(0대25％)(P=0.013).동태근종20례환자,림상완해후미재검출CEBPA기인돌변,이복발환자칙반유동양적위점돌변.PCR편단장도분석여측서분석결과적부합솔위100％.결론 CEBPA기인돌변시AML환자상견적분자돌변류형,CEBPA기인돌변환자적림상특정화질병상태유관,기돌변검측가작위AML환자질병상태적감측지표지일;M5형CEBPA단돌변환자경역반수NPM1돌변.
Objective 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.
