伴t(8;21)M2型急性髓系白血病患者c-kit和JAK2基因突变分析

目的 研究伴t(8;21)M2型成人急性髓系白血病(AML)患者蛋向酪氨酸激酶家族中c-kit和JAK2基因突变的发生情况、临床特征与预后的关系.方法 采用PCR扩增产物直接测序法检测78例伴t(8;21)M2患者中c-kit基因8号与17号外显子的突变情况;采用等位基因特异性PCR方法 检测患者JAK2 V617F的发生情况.结果 ①78例伴t(8;21)M2患者中27例(34.6%)检测出c-kit基因突变(mac-kit),6例(7.7%)检出JAK2 V617F突变,未见同一患者同时发生mac-kit和JAK2V617F突变. ②c-kit/JAK2 V617F突变型患者的外周血白细胞中位数为23.0(4.4～167.0)×109/L,明显高于野生型c-kit和JAK2患者14.4(1.6-97.4)×109/L](P<0.05),两组的血红蛋白水平、血小板计数、骨髓原始细胞比例、CD117表达水平以及年龄、性别差异均无统计学意义(P>0.05);c-kit突变型组患者的外周血白细胞中位数为23.1(4.4-167.0)×109/L,与野生型组16.0(1.6-97.4)×109/L]患者相比,差异有统计学意义(P<0.05);由于JAK2 V617F突变患者仅6例,未单独进行统计学分析. ③c-kit/JAK2 V617F突变组患者的完全缓解率与野生型组相近(分别69.6%与80.0%,P>0.05),但c-kit/JAK2 V617F突变组患者的2年持续完全缓解(CCR)率低于野生型组(分别26.7%与56.1%,P<0.05);两组患者2年总生存率的差异无统计学意义(分别为34.8%与58.6%,P>0.05).结论 蛋白酪氨酸激酶家族的c-kit和JAK2基因突变在伴t(8;21)M2型AML患者中较常见,并且与白细胞数量增高相关;其中c-kit突变更为频繁,但同一类的两种突变一般不会同时出现于同一患者;伴有此类基因突变的患者复发率高,预后较差;筛查此类基凶突变对于今后的靶向治疗以及了解临床预后将有重要意义.

Analysis of c-kit and JAK2 gene mutations in t(8;21 ) acute myeloid leukemia

Objective To evaluate the prevalence of c-kit and JAK2 gene mutations in protein tyrosine kinase(PTK) family in adult t(8 ;21 ) acute myeloid leukemia (AML) and their implications.Methods Genomic DNAs from 78 t(8 ;21 ) AML patients were screened for mutated c-kit(mutKIT) in exon 8 and 17 by PCR and sequencing.JAK2 V617F mutation screening was processed by allele-specific PCR.Results ①Among 78 t(8;21 ) AML patients,27(34.6% ) had muc-kit/JAK2 and 6(7.7% ) had JAK2 V617F,and none had both.②Peripheral WBC count was higher in mutKIT/JAK2 V617F patients than in wide-type c-kit/JAK2 (wtKIT/JAK2) patients (36.2±37.7)×109/L vs (21.7±21.1)×109/L] (P ＜0.05).There was no significant difference in hemoglobin level,platelet counts,percentage of blast cell in bone marrow,CD117 expression level,the age of onset and gender between the two groups.Peripheral WBC count was higher in mutKIT patients (38.8±40.7)×109/L] than in wtKIT patients (22.0±20.4)×109/L ] (P＜0.05).③Complete remission(CR) rates between patients with mutkit/JAK2 V617F and with wtKIT/JAK2 were similar(69.6% vs 80.0%,P ＞0.05),but the 2 year continuous CR(CCR) rate was lower in patients with mutKIT/JAK2 V617F (26.7% vs 56.1%,P ＜ 0.05 ).However,there was no significant difference in OS between mutKIT/JAK2 V617F and wtKIT/JAK2patients (34.8% vs 58.6%,P ＞0.05 ).Conclusions Occurrence of c-kit and JAK2 gene mutations especially c-kit mutation is common in t(8 ;21 ) AML patients,and is associated with higher WBC.These mutations confer higher relapse risk and predict poor prognosis.