核心结合因子相关性急性髓系白血病常见基因突变和细胞遗传学分析解析

核心结合因子（CBF）相关性急性髓系白血病（AML）是指一组以t（8；21）和inv（16）／t（16；16）异常为特征的白血病亚型，占AML的15 %，具有独特的临床及生物学特征，通常认为预后良好，给予大剂量阿糖胞苷（Ara-C）强化巩固治疗可以使患者获得长期生存。尽管如此，仍然有约50 %的患者复发，远期生存率仅50 %左右［1 ］，提示一些患者可能伴有不良的遗传学表型。c-Kit、FLT3、N-ras基因突变可协同作用，共同构成“二次打击”，导致这一类型白血病的发生。近年来同属于Ⅲ型家族的FLT3、c-Kit基因突变已

核心结合因子相关性急性髓系白血病

常见基因突变和细胞遗传学分析

冯雅青杨永平张艳芳刘喜张利东

037008 山西省大同市第三人民医院血液科

通信作者：冯雅青，Email:yaqing3@

DOI：10.3760/cma.j.issn.1009-9921.2016.07.004

【摘要】目的研究核心结合因子相关性急性髓系白血病（CBF-AML）c-Kit、FLT3基因突变发生情

况及患者的核型特征。方法采用基因组DNA聚合酶链反应（PCR）法结合碱基测序方法，检测48例

CBF-AML患者初诊时c-Kit、FLT3基因内部串联重复（ITD）突变和FLT3第二酪氨酸激酶结构域（TKD）点

突变发生情况及核型特征变化。结果48例CBF-AML患者中，13例（27.1%）出现c-Kit错义突变，包括

8号外显子突变5例，17号外显子突变8例。t（8；21）AML患者c-Kit基因突变发生率高于inv（16）AML

患者［33.3%（9／27）比19.0%（4／21），P＜0.05］。1例（2.1%）患者FLT3-ITD突变，3例（6.3 ％）患者FLT3-

TKD突变。RUNX1-RUNX1T1阳性附加染色体异常的发生率达25.9%（7／27），其中性染色体缺失最为常

见，CBFβ-MYH11阳性附加染色体异常发生率较低。结论在CBF-AML中c-Kit基因突变发生率高，

RUNX1-RUNX1T1阳性的附加染色体异常易见，为研究个体化治疗提供了一定的参考。

【关键词】白血病，髓样，急性；核心结合因子类；c-Kit；FLT3；细胞遗传学

基金项目：山西省科技攻关项目（20140313011-1）

Analysis of common gene mutations and cytogenetics in core binding factor related acute myeloid

leukemia Feng Yaqing，Yang Yongping，Zhang Yanfang，Liu Xi，Zhang Lidong

Department of Hematology，the Third People's Hospital of Datong City，Datong037008，China

Corresponding author:Feng Yaqing，Email:yaqing3@

【Abstract】Objective To assess the prevalence of c-Kit and FLT3gene mutations in core binding

factor related acute myeloid leukemia(CBF-AML)and analyze the karyotype characteristics of the CBF-AML

patients.Methods Mutations of c-Kit,FLT3-ITD and FLT3-TKD were detected by genomic DNA PCR and

sequencing,and the karyotype changes were analyzed in48newly diagnosed CBF-AML patients.Results

c-Kit aberrations were detected in13(27.1%)out of48patients,including5cases with exon8mutation and8

cases with exon17mutation.c-Kit was more prominent in t(8；21)AML patients than in inv(16)AML patients

[(33.3%(9/27)vs19.0%(4/21),P＜0.05].Only1case(2.1%)had FLT3-ITD mutation(FLT3-ITD+)and3

cases(6.3%)had FLT3-TKD mutation(FLT3-TKD+).Prevalence of RUNX1-RUNX1T1with additional

chromosome abnormality was as high as25.9%(7/27),in which sex chromosome elimination was the most

common one,while prevalence of CBFβ-MYH11with additional chromosome abnormality was low.

Conclusion c-Kit gene mutations and RUNX1-RUNX1T1additional chromosome abnormalities are common

in patients with CBF-AML and would be helpful for individualized treatment studies.

【Key words】Leukemia,myeloid,acute；Core binding factor；c-Kit；FLT3；Cytogenetics

Fund program：Science and Technology Research Project of Shanxi Province（20140313011-1）

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