原发性血小板增多症患者钙网蛋白基因突变及其与临床疗效的相关性

Detection of CALR gene mutation in patients with essential thrombocythemia and its correlation with clinical efficacy

目的检测原发性血小板增多症(ET)患者钙网蛋白(CALR)基因突变情况,评价其与临床疗效的相关性。方法采用PCR及其产物直接测序法检测ET患者CALR基因第9号外显子的突变情况,回顾性分析61例接受常规方案治疗的ET患者临床资料。结果 CALR基因第9号外显子突变阳性在JAK2V617F突变阴性的ET患者中检出率较高(51.4%)。其中以1型(52bp缺失)最多见,占总突变83.3%;其次为2型(5bp插入),占总突变11.1%。相较于JAK2V617F突变阳性及JAK2V617F、CALR突变双阴性的ET患者,CALR突变阳性的ET患者初诊时年龄更小、危险度更低(P<0.05)。基于羟基脲及干扰素的常规临床治疗方案能使较多的JAK2V617F突变阳性及CALR突变阳性患者获得完全或部分血液学缓解,相较于双阴性患者总缓解率更高。结论 CALR基因9号外显子突变是ET患者重要分子遗传学标志之一,基于羟基脲及干扰素的常规临床治疗方案能使具有CALR基因突变的患者获得较好的血液学反应。

Objective To detect the frequency of calreticulin(CALR)gene mutation in patients with essential thrombocytosis(ET)and evaluate its correlation with clinical efficacy.Methods PCR and its direct sequencing were used to detect the mutation of exon 9 of CALR gene in ET patients.The clinical data of 61 patients with ET who received conventional regimen were retrospectively analyzed.Results The total mutations of CALR gene exon 9 in JAK2V617F(-)ET patients was 51.4%.Among them,type 1(52 bp deletion)was the most common,accounting for 83.3%of the total mutation;followed by type 2(5 bp insertion),accounting for 11.1%of the total mutation.Compared with JAK2V617F(+)and double-negative mutation ET patients,CALR(+)patients with ET were younger(P<0.05)and less dangerous(P<0.05)at the time of initial diagnosis.Conventional clinical treatment based on hydroxyurea and interferon enable more patients with JAK2V617F(+)or CALR(+)to achieve complete or partial hematologic remission when compared with double-negative ET patients.Conclusion The mutation of exon 9 of CALR gene is one of the important molecular genetic markers of ET patients.The conventional clinical treatment based on hydroxyurea and interferon can obtain good hematologic response in patients with mutation of CALR gene.