中文摘要：

目的研究酪氨酸激酶（TK）相关基因c—Kit、FLT3、JAK2V617F突变在核心结合因子相关性急性髓系白血病（CBF—AML）中的发生情况及其对患者临床特征及预后的影响。方法采用基因组DNA．PCR法结合碱基测序，检测58例CBF—AML患者[其中30例为伴t（8；21）异常，28例为伴inv（16）异常]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）的点突变发生情况；JAK2V617F突变应用等位基因特异性PCR方法检测。随访观察各种突变对患者临床特征及预后的影响。结果58例CBF—AML患者中19例出现c-Kit错义突变，其中包括6例8号外显子突变（mutKIT8）和13例17号外显子突变（mutKIT17）。mutKIT8在伴inv（16）患者中更多见。2例患者FLT3-ITD突变阳性（FLT3-ITD＋），7例（12．1％）患者FLT3-TKD突变阳性（FLT3-TKD＋）。58例初治CBF—AML患者均未检出JAK2V617F。受体酪氨酸激酶（RTK）突变的累计发生率达46．6％（58例中27例），仅有1例患者同时发生2种错义突变（FLT3-TKD＋和mutKIT8）。和c—Kit基因野生型患者相比，mutKIT17患者中位发病年龄明显升高（分别为31岁和55岁，P=0．003）。c—Kit突变导致患者总生存（OS）率及持续完全缓解（CCa）率降低（P=0．053和P=0．048）；其中存在mutKIT17的患者OS率及CCR率降低更为明显（P=0．005和P=0．013）。FLT3-TKD突变对CBF—AML患者的预后无明显影响。结论在CBF—AML中RTK突变常见，但同属一类的两种基因突变极少存在于同一患者。在CBF—AML中c—Kit基因突变发生频繁；JAK2V617F突变罕见。c—Kit突变患者，尤其是rout-KIT17患者发病年龄明显增高、易复发、预后差。

英文摘要：

Objective To assess the prevalence of several tyrosine kinases （TKs） gene mutations including c-Kit, FLT3 and JAK2 V617F in core binding factor related acute myeloid leukemia （CBF-AML） , and analyze their impact on clinical characteristics and prognosis. Methods Mutations of c-Kit, FLT3-ITD and FLT3-TKD were detected by genomic DNA PCR and sequencing, and JAK2 V617F mutation screening by allele-specific PCR in 58 newly diagnosed CBF-AML patients [ 28 AML with inv（16） and 30 with t （8;21） ], and analyze the patients clinical characteristics and prognoses. Results c-Kit aberrations were detected in 32.8% cases, including 6 cases mutated in exon 8 （mutKIT8） and 13 mutated in exon 17 （mutKIT17）. MutKIT8 was more prominent in inv（16） than in t（8;21 ） patients （21.4% vs 0, P =0.009）. Only 2 cases had FLT3-ITD and 7 （ 12.1% ） FLT3-TKD mutations. The result of JAK2 V617F mutation screenings in these CBF-AML patients was negative. The frequency of receptor tyrosine kinases （RTK） mutations was 46.6% and only one case had two kinds of missense mutations （ mutKIT8 ＆ TKD ＋ ）. Median age of onset was higher for mutKITl7 than for wide-type c-Kit （wtKIT） patients （55 vs 31, P = 0. 003 ）. c-Kit mutations were significantly associated with decreased overall survival（OS） and continuous complete remission （CCR） rates （P = 0. 053, and 0. 048 respectively）, and so did more for exon17 mutated patients reduced （P=0. 005, and 0.013 respectively ）. FLT3-TKD mutation showed no effects on prognosis of CBF-AML patients. Condusions RTK mutations are common in patients with CBF-AML. c-Kit mutations frequently and JAK2V617F mutation rarely appear in CBF-AML. c-Kit mutations, especially mutKIT17 confers higher relapse risk and poorer prognosis.