CAJ | 학술논문

目的研究酪氨酸激酶(TK)相关基因c-Kit、FLT3、JAK2 V617F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；JAK2 V617F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JAK2 V617F.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(CCR)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；JAK2 V617F突变罕见.c-Kit突变患者,尤其是mutKIT17患者发病年龄明显增高、易复发、预后差.
목적 연구락안산격매(TK)상관기인c-Kit、FLT3、JAK2 V617F돌변재핵심결합인자상관성급성수계백혈병(CBF-AML)중적발생정황급기대환자림상특정급예후적영향.방법 채용기인조DNA-PCR법결합감기측서,검측58례CBF-AML환자[기중30례위반t(8;21)이상,28례위반inv(16)이상]초진시c-Kit、FLT3기인내부천련중복(ITD)돌변화FLT3제이락안산격매결구역(TKD)적점돌변발생정황；JAK2 V617F돌변응용등위기인특이성PCR방법검측.수방관찰각충돌변대환자림상특정급예후적영향.결과 58례CBF-AML환자중19례출현c-Kit착의돌변,기중포괄6례8호외현자돌변(mutKIT8)화13례17호외현자돌변(mutKIT17).mutKIT8재반inv(16)환자중경다견.2례환자FLT3-ITD돌변양성(FLT3-ITD+),7례(12.1％)환자FLT3-TKD돌변양성(FLT3-TKD+).58례초치CBF-AML환자균미검출JAK2 V617F.수체락안산격매(RTK)돌변적루계발생솔체46.6％(58례중27례),부유1례환자동시발생2충착의돌변(FLT3-TKD+화mutKIT8).화c-Kit기인야생형환자상비,mutKIT17환자중위발병년령명현승고(분별위31세화55세,P=0.003).c-Kit돌변도치환자총생존(OS)솔급지속완전완해(CCR)솔강저(P=0.053화P=0.048)；기중존재mutKIT17적환자OS솔급CCR솔강저경위명현(P=0.005화P=0.013).FLT3-TKD돌변대CBF-AML환자적예후무명현영향.결론 재CBF-AML중RTK돌변상견,단동속일류적량충기인돌변겁소존재우동일환자.재CBF-AML중c-Kit기인돌변발생빈번；JAK2 V617F돌변한견.c-Kit돌변환자,우기시mutKIT17환자발병년령명현증고、역복발、예후차.
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 V617 F 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 mutKIT17 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.Conclusions 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.