原发性骨髓纤维化患者症状评分与危险度分层及基因突变的关系

Symptom burden and its relationships with risk assessment and gene mutations in patients with primary myelofibrosis

目的 初步探讨原发性骨髓纤维化（PMF）患者的症状评分与危险度分层及基因突变的关系.方法 对2012年3月至2015年4月中日友好医院诊治的PMF患者用骨髓增殖性肿瘤（MPN） 10症状评分表进行症状评分,同时用动态国际预后积分系统加强版（DIPSS-plus）进行危险度分层,检测患者的多种MPN相关基因突变,分析患者症状评分与危险度分层和基因突变的关系.结果 36例患者中25例患者进行了MPN 10症状评分,平均22.8分,乏力及无活动力发生率最高,均为22例（88％）,而发热、骨痛少见,分别为3例和5例.36例患者中35例用DIPSS-plus进行了危险度分层,分别为低危7例（20％）,中危-17例（20％）,中危-2 4例（11.4％）,高危17例（48.6％）.25例接受症状评分的患者中,中危-1组症状评分为（28.7±6.2）分,高于中危-2组的（11.0±2.9）分（t=2.579,P=0.038）;中危-2组平均分低于高危组的（26.4±3.2）（t=2.650,P=0.024）.34例进行基因突变检测的患者中,JAK2阳性25例（73.5％）,其他发生频率较高的基因突变依次是CALR、ASXL1、U2AF1、SRSF2、TET2、SETBP1和UTX.TET2突变发生率在低中危组和高危组中差异有统计学意义（P=0.022）;携带3种及以上基因突变患者的症状评分高于携带3种以下或未携带基因突变的患者（P=0.011）.结论 PMF患者的症状可能反映了PMF的异质性和预后差异.PMF症状评分可能与DIPSS-plus危险度分层和基因突变数存在一定关联,TET2突变与PMF进展可能存在关联.

Objective To study the symptom burden and its relationships with risk assessment and gene mutations in patients with primary myelofibrosis （PMF）.Methods The symptom burden of patients with PMF was assessed in China-Japan Friendship Hospital from Mar 2012 to Apr 2015 by using MPN10 and also Dynamic International Prognostic Scoring System-plus （DIPSS-plus）.Several related gene mutations in these patients were detected,and the relationships among the symptom burden,DIPSS-plus and gene mutations were analyzed.Results Among 36 patients,the symptom burden was assessed in 25 patients with average score 22.8.Fatigue and inactivity were occurred similarly in 22 cases （88 %）,and fever and bone pain were only in 3 cases and 5 cases,respectively.According to DIPSS-plus,35 patients were stratified into low （7 cases,20.0 %）,intermediate-1 （7 cases,20.0 %）,intermediate-2 （4 cases,11.4 %） and high-risk groups （17 cases,48.6 %）.25 patients completed MPN10.Total symptom score in intermediate-1 group was 28.7±6.2,which was higher than that in intermediate-2 group （11.0±2.9） （t =2.579,P =0.038）,and the score in intermediate-2 group was lower than that in high-risk group （26.4±3.2） （t =2.650,P =0.024）.Among 34 patients who received gene mutation detection,25 cases （73.52 %） were identified as JAK2 mutation,and others were CALR,ASXL1,U2AF1,SRSF2,TET2,SETBP1 and UTX mutations.The incidence of TET2 mutation had significant difference between low-/intermediate-risk group and high-risk group （P =0.022）.The symptom score of patients who carried 3 or more mutations was significantly higher than that of less 3 mutations （P =0.011）.Conclusions The symptom burden of patients with PMF may reflect the heterogeneity and prognostic difference of PMF,and could be associated with DIPSS-plus risk stratification and the number of gene mutations.TET2 mutation is probably associated with PMF progress.