中国年轻骨髓增殖性肿瘤患者的临床和基因突变特征

Clinical and genetic characteristics of young patients with myeloproliferative neoplasms

目的探究中国年轻骨髓增殖性肿瘤(MPN)患者的临床和基因突变特征。方法通过横断面研究,在全国范围内向MPN患者发放调查问卷,根据诊断时年龄分为年轻组(≤40岁)、中年组(41~60岁)和老年组(>60岁),在各疾病类型中比较三组的差异。结果共收集到1727份可供分析的问卷,其中年轻组453例(26.2%),包括原发性血小板增多症(ET)274例、真性红细胞增多症(PV)80例、骨髓纤维化(MF)99例(原发性MF 45例,PV后MF 20例,ET后MF 34例);男性178例(39.3%),中位年龄31(18~40)岁。与中年、老年MPN受访者相比,年轻MPN受访者中未婚、高学历、无合并症、无合并用药、较低危险度分层占比较高(P<0.001)。年轻MPN受访者中以头痛为首发症状患者占比较高(ET:P<0.001;PV:P=0.007;MF:P=0.001),脾大的比例在初诊(PV:P<0.001)和调研时(ET:P=0.052;PV:P=0.063)最高,而血栓事件的发生率在初诊(ET:P<0.001;PV:P=0.011)和调研时(ET:P<0.001;PV:P=0.003)均最低。年轻MPN受访者JAK2突变比例最低(ET:P<0.001;PV:P<0.001;MF:P=0.013),CALR突变比例最高(ET:P<0.001;MF:P=0.015),非驱动基因突变(ET:P=0.042;PV:P=0.043;MF:P=0.004)和高分子风险(HMR)突变(ET:P=0.024;PV:P=0.023;MF:P=0.001)的检出率均最低。结论与中、老年患者相比,年轻MPN患者有着特有的临床表现和基因突变特征。

Objectives To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms(MPN).Methods In this cross-sectional study,anonymous questionnaires were distributed to patients with MPN patients nationwide.The respondents were divided into 3 groups based on their age at diagnosis:young(≤40 years),middle-aged(41-60 years),and elderly(>60 years).We compared the clinical and genetic characteristics of three groups of MPN patients.Results 1727 assessable questionnaires were collected.There were 453(26.2%)young respondents with MPNs,including 274 with essential thrombocythemia(ET),80 with polycythemia vera(PV),and 99 with myelofibrosis.Among the young group,178(39.3%)were male,and the median age was 31(18-40)years.In comparison to middle-aged and elderly respondents,young respondents with MPN were more likely to present with a higher proportion of unmarried status(all P<0.001),a higher education level(all P<0.001),less comorbidity(ies),fewer medications(all P<0.001),and low-risk stratification(all P<0.001).Younger respondents experienced headache(ET,P<0.001;PV,P=0.007;MF,P=0.001)at diagnosis,had splenomegaly at diagnosis(PV,P<0.001),and survey(ET,P=0.052;PV,P=0.063).Younger respondents had fewer thrombotic events at diagnosis(ET,P<0.001;PV,P=0.011)and during the survey(ET,P<0.001;PV,P=0.003).JAK2 mutations were found in fewer young people(ET,P<0.001;PV,P<0.001;MF,P=0.013);however,CALR mutations were found in more young people(ET,P<0.001;MF,P=0.015).Furthermore,mutations in non-driver genes(ET,P=0.042;PV,P=0.043;MF,P=0.004)and high-molecular risk mutations(ET,P=0.024;PV,P=0.023;MF,P=0.001)were found in fewer young respondents.Conclusion Compared with middle-aged and elderly patients,young patients with MPN had unique clinical and genetic characteristics.