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

作　　者：张梦雨 宝梅 石红霞[1] 刘晓力[2] 许娜[2] 段明辉[3] 庄俊玲[3] 杜新[4] 秦玲[5] 惠吴函[6] 梁蓉 王梅芳[8] 陈烨[9] 李冬云[10] 杨威[11] 唐古生 张伟华[13] 匡霞 苏伟[15] 韩艳秋[16] 陈丽梅[17] 许霁虹[18] 刘卓刚[11] 黄健 赵春亭[20] 佟红艳[21] 胡建达[22] 陈春燕[23] 陈协群 肖志坚 江倩[1] Zhang Mengyu;Bao Mei;Shi Dayu;Shi Hongxia;Liu Xiaoli;Xu Na;Duan Minghui;Zhuang Junling;Du Xin;Qin Ling;Hui Wuhan;Liang Rong;Wang Meijfang;Chen Ye;Li Dongyun;Yang Wei;Tang Gusheng;Zhang Weihua;Kuang Xia;Su Wei;Han Yanqiu;Chen Limei;Xu Jihong;Liu Zhuogang;Huang Jian;Zhao Chunting;Tong Hongyan;Hu Jianda;Chen Chunyan;Chen Xiequn;Xiao Zhijian;JiangQian(Peking University People's Hospital,Bejing 100044,China;Nanfang Hospital,Southern Medical University,Guangzhou 510080,China;Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China;Department of Hematology,Shenzhen Second People's Hospital(First Affiliated Hospital of Shenzhen University),Shenzhen 518035,China;The First Afiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology,Zhenzhou 471003,China;Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Xi Jing Hospital,The Fourth Military Medical University,Xi'an 710032,China;Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Shengjing Hospital Affiliated to China Medical University,Shenyang l10020,China;Department of Hematology,Institute of Hematology,The First Affiliated Hospital of Naval Medical University,Changhai Hospital,Shanghai 200433,China;First Hospital of Shanxi Medical University,Taiyuan 300012,China;Kaifeng Central Hospital,Kaifeng 475000,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China;The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China;The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China;Department of Hematology,the First Hospital of Qiqihar,Qiqihar 161005,China;The Fourth Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 322000,China;The Affiliated Hospital of Qingdao University,Qingdao 266003,China;The First Affiliated Hospital of College of Medicine,Zhejiang University,H

机构地区：[1]北京大学人民医院,北京大学血液病研究所,国家血液系统疾病临床医学研究中心,北京100044 [2]南方医科大学南方医院血液科,广州510080 [3]中国医学科学院、北京协和医学院北京协和医院血液内科,北京100730 [4]深圳市第二人民医院(深圳大学附属第一医院)血液科,深圳518035 [5]河南科技大学第一附属医院河南科技大学临床医学院,郑州471003 [6]首都医科大学宣武医院血液科,北京100053 [7]空军军医大学西京医院血液科,西安710032 [8]山西医科大学第二医院血液科,太原030001 [9]首都医科大学附属北京安贞医院血液科,北京100029 [10]北京中医药大学东直门医院血液肿瘤科,北京100700 [11]中国医科大学附属盛京医院血液科,沈阳110020 [12]海军军医大学第一附属医院(上海长海医院)血液科,中国人民解放军血液病研究所,上海200433 [13]山西医科大学第一医院血液科,太原300012 [14]开封市中心医院血液科,开封475000 [15]北京中医药大学东方医院血液病科,北京100078 [16]内蒙古医科大学附属医院血液内科,呼和浩特010050 [17]西安交通大学第一附属医院血液内科,西安710061 [18]齐齐哈尔市第一医院血液内科,齐齐哈尔161005 [19]浙江大学医学院附属第四医院血液内科,杭州322000 [20]青岛大学附属医院血液科,青岛266003 [21]浙江大学医学院附属第一医院血液科,杭州310003 [22]福建医科大学附属协和医院血液内科,福州350001 [23]山东大学齐鲁医院血液科,济南250012 [24]西北大学医学院,西安710069 [25]中国医学科学院血液病医院(中国医学科学院血液学研究所),实验血液学国家重点实验室,国家血液系统疾病临床医学研究中心,天津300020

出　　处：《中华血液学杂志》2023年第3期193-201,共9页Chinese Journal of Hematology

基　　金：国家自然科学基金(81970140)。

摘　　要：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.

关 键 词：骨髓增殖性肿瘤 临床表现 基因突变 NGS分析 

分 类 号：R733.3[医药卫生—肿瘤]