高嗜酸性粒细胞综合征及慢性嗜酸性粒细胞白血病的靶向测序研究  

Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia

作　　者：曲士强 秦铁军 徐泽锋 张悦 贾玉娇 艾小飞 张宏丽 方力维 胡耐博 潘丽娟 李冰 刘晋琴 汝昆 肖志坚 Qu Shiqiang;Qin Tiejun;Xu Zefeng;Zhang Yue;Jia Yujiao;Ai Xiaofei;Zhang Hongli;Fang LiweL Hu Naibo;Pan Lijuan;Li Bing;Liu Jinqin;Ru Kun;Xiao Zhijian(Institute of Hematology and Blood Diseases Hospital Chinese Academe of Medical Sciences＇, The State Key Laboratory of Experimental Hematology, Tianjin 300020, Chin)

机构地区：[1]中国医学科学院、北京协和医学院血液病医院(血液学研究所)、实验血液学国家重点实验室,天津300020

出　　处：《中华血液学杂志》2018年第6期501-506,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金（81470295、81530008、81370611、81600098、81270585）;天津市自然科学基金（16JCQNJC11400）;中国医学科学院医学与健康科技创新工程项目（2016-I2M-1-001）;协和学者与创新团队发展计划

摘　　要：目的分析嗜酸性粒细胞增多症的分子学特征。方法对24例伴PDGFRA、PDGFRB或FGFR1重排的慢性嗜酸性粒细胞白血病（CEL）及62例高嗜酸性粒细胞综合征（HES）患者进行靶向测序，利用权威数据库进行变异注释及氨基酸突变分析，推测可能致病性突变。结果17例（71％）CEL患者检出37种克隆性异常，但未发现重现性突变位点及热点突变区域，19例伴PDGFRA重排患者未检出致病性突变，2例进展为急性髓系白血病的伴FGFR1重排患者及1例进展为T淋巴母细胞淋巴瘤的伴PDGFRB重排患者分别检出ASXL1、RUNX1和NRAS的致病性突变。49例（71％）HES患者检出102种克隆性异常，主要热点突变区域包括：CEBPAExon1、TET2Exon3、ASXL1Exon12、IDH1Y208C和FGFR3L164V。其中2例经伊马替尼单药治疗获得血液学缓解的HES患者分别检出CRRLF2P224L和PDGFRBR370C点突变。结论伴PDGFRA、PDGFRB或FGFR1重排的CEL致病因素单一，疾病进展可能有其他突变参与。HES可能由具有热点突变区域的多种基因参与致病，部分突变位点对酪氨酸激酶抑制剂治疗敏感。Objective Analysis of the molecular characteristics of eosinophilia. Methods Targeting sequence to 24 patients with chronic eosinophilic leukemia （CEL） with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome （HES）. Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included： CEBPA Exonl, TET2 Exon3, ASXL1 Exonl2, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion Thepathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.

关 键 词：嗜酸粒细胞增多 白血病  嗜酸粒细胞  慢性 高嗜酸性粒细胞综合征 靶向测序 

分 类 号：R55[医药卫生—血液循环系统疾病] R733.72[医药卫生—内科学]