CAJ | 학술논문

目的研究原发性血小板增多症(ET)患者CALR基因突变情况,比较其与JAK2V617F、MPL W515K突变及三种突变阴性患者部分临床参数的差异.方法采用基因组DNA-PCR扩增产物直接测序法检测150例ET患者CALR基因9号外显子及MPL W515K突变;采用等位基因特异性PCR检测JAK2 V617F突变检出情况.结果 ①150例ET患者中共检出CALR突变38例(25 3％),Ⅰ型(c.1092_1143de152bp) 17例,Ⅱ型(c.1154_ 1155insTTGTC) 16例,Ⅲ型(c.1094_ 1139de146bp)4例,Ⅳ型(c.1103_1136de134bp)1例.②JAK2 V617F和MPL W515K的突变检出率分别为61.3％(92/150)和2.7％(4/150);54例JAK2 V617F及MPL W515K突变阴性患者中CALR突变检出率为70.4％(38/54),未检测到任何两种基因突变共存.③CALR突变组的外周血白细胞和血红蛋白水平低于JAK2V617F突变组(P＜0.05),中位年龄为59(29～89)岁,高于三种突变阴性组的29.5 (16～67)岁(P＜0.01);147例患者有染色体核型分析结果,其中4例存在核型异常,异常核型与正常核型患者中CALR基因突变检出率分别为75.0％(3/4)、24.5％ (35/143),差异有统计学意义(P=0.019).结论 CALR突变在JAK2 V617F及MPL W515K突变阴性的ET患者中有较高的检出率,并与异常核型相关;CALR突变组外周血白细胞和血红蛋白水平低于JAK2 V617F突变组.
목적 연구원발성혈소판증다증(ET)환자CALR기인돌변정황,비교기여JAK2V617F、MPL W515K돌변급삼충돌변음성환자부분림상삼수적차이.방법 채용기인조DNA-PCR확증산물직접측서법검측150례ET환자CALR기인9호외현자급MPL W515K돌변;채용등위기인특이성PCR검측JAK2 V617F돌변검출정황.결과 ①150례ET환자중공검출CALR돌변38례(25 3％),Ⅰ형(c.1092_1143de152bp) 17례,Ⅱ형(c.1154_ 1155insTTGTC) 16례,Ⅲ형(c.1094_ 1139de146bp)4례,Ⅳ형(c.1103_1136de134bp)1례.②JAK2 V617F화MPL W515K적돌변검출솔분별위61.3％(92/150)화2.7％(4/150);54례JAK2 V617F급MPL W515K돌변음성환자중CALR돌변검출솔위70.4％(38/54),미검측도임하량충기인돌변공존.③CALR돌변조적외주혈백세포화혈홍단백수평저우JAK2V617F돌변조(P＜0.05),중위년령위59(29～89)세,고우삼충돌변음성조적29.5 (16～67)세(P＜0.01);147례환자유염색체핵형분석결과,기중4례존재핵형이상,이상핵형여정상핵형환자중CALR기인돌변검출솔분별위75.0％(3/4)、24.5％ (35/143),차이유통계학의의(P=0.019).결론 CALR돌변재JAK2 V617F급MPL W515K돌변음성적ET환자중유교고적검출솔,병여이상핵형상관;CALR돌변조외주혈백세포화혈홍단백수평저우JAK2 V617F돌변조.
Objective To explore the prevalence of CARL gene mutations and the mutation types in patients with essential thrombocythemia (ET),and to compare the patients clinical characteristics of CALR mutation with JAK2 V617F,MPL W515K mutation patients and triple negative group.Methods The mutations of CALR gene at extron 9 and MPL W515K in 150 ET patients were detected by PCR amplification followed by direct sequencing of genomic DNA,the JAK2 V617F mutation by using allele specific PCR.Results ①The CALR mutations were found in 38 patients (25.3％) of 150 ET patients.A total of 4 types of CALR mutations were identified (type Ⅰ c.1092_1143de152bp,n=17;type Ⅱ c.1154_ 1155insTTGTC,n=16;type Ⅲ c.1094_1139de146bp,n=4;type Ⅳ c.1103_1136de134bp,n=1).②The incidence of JAK2 V617F and MPL W515K was 61.3％ (92/150) and 2.7％ (4/150),respectively.The frequency of CALR mutation was 70.4％ (38/54) in 54 ET patients without JAK2 V617F and MPL W515K mutations.The co-occurrence of any two kinds of gene mutations was not detected.③The hemoglobin level and leukocyte counts of patients with CARL mutations were significantly lower than that in patients with JAK2 V617F mutations (P＜0.05).The median age of patients with CALR mutation was significantly higher than that of triple negative patients (59 years vs 29.5 years,P＜0.01).Cytogenetic analysis was performed in 147 patients,and there were 4 abnormal karyotype cases.CALR mutation incidence was significantly higher in abnormal karyotype cases than that in normal ones (75％ vs 24.5％,P=0.019).Conclusions The incidence of CALR mutations is high in ET patients without JAK2 V617F and MPL W515K mutations,and is associated with abnormal karyotype.CARL-mutated cases showed a significantly lower leucocyte and hemoglobin levels compared with JAK2 V617F mutated cases.