成人NUP98融合基因阳性AML患者的临床特点及生物学特征  

Molecular Characteristics and Clinical Features of Adults with NUP98 Fusions in Acute Myeloid Leukemia

作　　者：伦燕 黄菁草 龙丹[2] 王方芳[1] 代阳[1] 杨艳[1] 赵婷婷[1] 李清 吴俣[1] LUN Yan;HUANG Jing-cao;LONG Dan;WANG Fang-fang;DAI Yang;YANG Yan;ZHAO Ting-ting;LI Qing;WU Yu(Department of Hematology,Sichuan University,Chengdu 610041,China;Key Laboratory of Transplant Engineering and Immunology,Ministry of Health,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院/华西临床医学院血液内科,成都610041 [2]四川大学华西医院移植工程与移植免疫重点实验室,成都610041

出　　处：《四川大学学报（医学版）》2018年第4期575-581,共7页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81470327);四川省科技厅科技支撑项目(No.2014SZ0202);四川省人力资源和社会保障厅2016年度省学术和技术带头人培养支持经费资助

摘　　要：目的探讨成人急性髓细胞白血病(AML)患者中核孔蛋白98(NUP98)融合基因阳性患者的临床特点及生物学特征,以及NUP98融合基因与AML常见融合基因、预后基因的共表达对AML预后的影响。方法收集四川大学华西医院2014年7月1日至2017年3月1日间住院的成人初发AML和骨髓增生异常综合征(MDS)患者的骨髓或外周血标本,检测NUP98融合基因,并检测AML患者染色体核型。将染色体11p15重排或NUP98相关融合基因阳性的AML患者作为研究组,此期间初诊的其余AML患者作为对照组,并将其分为低、中、高危对照组。通过对照研究,分析其血液学特点、完全缓解率(CR)、与预后基因的共表达率以及生存分析。结果样本总量为197例。共16例(8.1%)患者存在NUP98相关融合基因(即研究组),发现我院首例NUP98-拓扑异构酶Ⅰ(TOP1)融合基因阳性AML。研究组患者按FAB分型,主要为M2和M5;研究组Fms样酪氨酸激酶-3(FLT3)-基因内部串联重复突变(ITD)发生率[31.25%(5/16)]和死亡率[80.00%(4/5)]高于对照组[发生率9.95%(19/181),死亡率42.11%(8/19),P<0.05];研究组诱导化疗获CR率为78.57%,高于总对照组及其中高、中危亚组(P<0.05)。研究组中位总生存期(OS)为13月,中位无白血病生存期(LFS)仅为5月。结论NUP98融合基因阳性AML易合并其它融合基因及预后基因的共表达,LFS和OS较短,尤其发生FLT3-ITD共表达时,死亡率高。Objective To determine the molecular characteristics and clinical features of patients with nucleoporin 98（NUP98）fusion gene positive acute myeloid leukemia（AML）and the impact of coexistence of NUP98 fusion genes and other prognosis-related genes.Methods Samples of bone marrow or peripheral blood were collected from the adult patients with de novo AML and myelodysplastic syndrome（MDS）in our hospital from July 1 st,2014 to March 1 st,2017.NUP98 fusuion genes and their karyotype were detected by PCR.The AML patients with chromosome 11 p15 rearrangement or NUP98 fusion genes were studied as the research group and the remaining AMLs in this period as the control group.Meanwhile,the control AML group was divided into low-risk,medium-risk and high-risk groups respectively.Through comparison,analyzing the hematological characteristics,CR rates,the frequency of coexpression with other prognosis-related genes,and over all survival were done between these NUP98 fusion gene positive AMLs and control.Results A total of 197 AML patients participated in this study,including 16（8.1%）having NUP98 fusion genes and the first case of positive NUP98-topoisomerase1（TOP1）fusion gene.The NUP98 positive AMLs were mainly M2 and M5 in FAB classifications.Fms-like tyrosine kinase-3（FLT3）-internal tandem duplication（ITD）（FLT3-ITD）occurred [31.25%（5/16）]and mortality[80.00%（4/5）]of the patients with NUP98 positive AMLs,higher than control group [occurred：9.95%（19/181）,mortality：42.11%（8/19）,P〈0.05].The CR rate of the study group induced chemotherapy was 78.57%,higher than the control group and the middle,high and middle rick control group.The median overall survival（OS）and leukemia free survival（LFS）of the patients with NUP98 positive AMLs were 13 months and 5 months,respectively.Conclusion NUP98 fusion positive AMLs have high level of coexistence with other prognostic-related genes,especially FLT3-ITD,leading to poor prognosis,short survival.

关 键 词：急性髓细胞白血病 NUP98-HOXA9 NUP98-NSD1 NUP98-TOP1 FLT3-ITD 

分 类 号：R733.71[医药卫生—肿瘤]