原发性髓系肉瘤遗传学和分子学改变的临床意义  

Clinical Significance of Genetic and Molecular Changes in Primary Myeloid Sarcoma

作　　者：江亚军 张春芳[2] 王红霞 赵兰 张飞飞 韩秀华 JIANG Ya-Jun;ZHANG Chun-Fang;WANG Hong-Xia;ZHAO Lan;ZHANG Fei-Fei;HAN Xiu-Hua(Department of Hematology,Jiading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences,Shanghai 201800,China;Department of Pathology,The First People's Hospital of Lianyungang,Lianyungang 222002,Jiangsu Province,China;Department of Pathology,Jiading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences,Shanghai 201800,China)

机构地区：[1]上海健康医学院附属嘉定区中心医院血液科,上海201800 [2]连云港市第一人民医院病理科,江苏连云港222002 [3]上海健康医学院附属嘉定区中心医院病理科,上海201800

出　　处：《中国实验血液学杂志》2024年第1期27-32,共6页Journal of Experimental Hematology

基　　金：嘉定区卫生健康委员会科研课题(2020-KY-06;2021-KY-ZYY-07)。

摘　　要：目的:探讨原发性髓系肉瘤遗传学和分子生物学改变的临床意义。方法:选择2010年9月-2021年12月于上海健康医学院附属嘉定区中心医院、连云港市第一人民医院诊断的14例原发性髓系肉瘤患者为研究对象,应用荧光原位杂交技术检测其AML1-ETO融合、PML-RARα融合、CBFβ断裂情况,应用下一代基因测序技术检测其NPM1、CEBPA、FLT3、RUNX1、ASXL1、KIT、TP53等基因突变情况。结果:14例患者的髓系肉瘤发生于骨、乳腺、附睾、肺、胸壁、宫颈、小肠、卵巢、淋巴结、中枢神经系统等组织器官,肿瘤细胞表达MPO(13例)、CD34(7例)、CD43(8例)、CD68(7例)、CD99(8例)、CD117(6例)。4例检测出细胞遗传学异常(AML1-ETO融合3例,CBFβ断裂1例),未检出PML-RARα融合。发生AML1-ETO融合/CBFβ断裂病例的总体生存期、无白血病生存期与未发生AML1-ETO融合/CBFβ断裂者比较差异均无统计学意义(P>0.05)。分别有5例、3例、5例、3例、2例、2例和1例患者发生NPM1、CEBPA、FLT3-ITD、RUNX1、ASXL1、KIT、TP53基因突变,其中7例至少发生FLT3-ITD、RUNX1、ASXL1、TP53基因中的一个突变。发生FLT3-ITD/RUNX1/ASXL1/TP53突变患者的总体生存期、无白血病生存期均明显短于未发生突变者(P<0.01)。结论:应用荧光原位杂交技术和下一代基因测序技术可以检出原发性髓系肉瘤的遗传学和分子学异常。FLT3-ITD/RUNX1/ASXL1/TP53突变提示预后更差,但仍需进一步临床研究证实。Objective:To investigate the clinical significance of genetic and molecular changes in primary myeloid sarcoma(MS).Methods:Fourteen patients with primary MS were selected in Jiading District Central Hospital Affiliated Shanghai University of Medicine&Health Sciences,The First People's Hospital of Lianyungang from September 2010 to December 2021.AML1-ETO fusion,PML-RARαfusion and CBFβbreakage were detected by fluorescence in situ hybridization(FISH),and the mutations of NPM1,CEBPA,FLT3,RUNX1,ASXL1,KIT and TP53 genes were detected by new generation sequencing(NGS).Results:Among 14 patients,the MS occurred in bone,breast,epididymis,lung,chest wall,cervix,small intestine,ovary,lymph nodes and central nervous system.The tumor cells expressed MPO(13 cases),CD34(7 cases),CD43(8 cases),CD68(7 cases),CD99(8 cases)and CD117(6 cases).Cytogenetic abnormalities were observed in 4 cases,including 3 cases of AML1-ETO fusion and 1 case of CBFβbreakage,while no PML-RARαfusion was detected.There were no significant differences in overall survival(OS)and leukemia-free survival(LFS)between patients with and without AML1-ETO fusion/CBFβbreakage(both P>0.05).Among the 14 patients,the number of NPM1,CEBPA,FLT3-ITD,RUNX1,ASXL1,KIT and TP53 gene mutations was 5,3,5,3,2,2,1,respectively,of which 7 cases had at least one mutation in FLT3-ITD,RUNX1,ASXL1 and TP53 gene.The OS and LFS of patients with FLT3-ITD,RUNX1,ASXL1 or TP53 mutation were shorter than those without mutations(both P<0.01).Conclusion:The genetic and molecular abnormalities of primary MS can be detected by FISH and NGS techniques.FLT3-ITD,RUNX1,ASXL1 or TP53 mutation indicates a worse prognosis,but further clinical studies are needed to confirm it.

关 键 词：髓系肉瘤 免疫组化 遗传学 分子生物学 预后 

分 类 号：R733.3[医药卫生—肿瘤]