获得性骨髓衰竭患者8号染色体三体的克隆演变及临床意义  

Clonal evolution and clinical significance of trisomy 8 in acquired bone marrow failure

作　　者：周立伟 施均 黄振东 聂能 邵英起 李星鑫 葛美丽 张静 金朋 黄金波 郑以州 Zhou Liwei;Shi Jun;Huang Zhendong;Nie Neng;Shao Yingqi;Li Xingxin;Ge Meili;Zhang Jing;Jin Peng;Huang Jinbo;Zheng Yizhou(Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China,State Key Laboratory of Experimental Hematology, Tianjin 300020, China)

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》2019年第6期507-511,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金(81370606、81670120).

摘　　要：目的分析获得性骨髓衰竭患者8号染色三体(+8)的克隆演变及其临床意义.方法回顾性分析2011年6月至2018年9月63例伴单纯+8染色体的获得性骨髓衰竭患者临床资料,总结克隆演变模式及其与免疫抑制治疗(IST)疗效的关系.结果63例患者中AA 39例,相对低危MDS 24例,男24例,女39例.MDS患者治疗前+8克隆负荷大于AA患者[65%(15%~100%)对25%(4.8%~100%),z=3.48,P=0.001].AA及MDS患者+8克隆大小<30%、30%~<50%、≥50%3组间的比例差异有统计学意义[AA分别为55.6%(20/36)、22.2%(8/36)、22.2%(8/36),MDS分别为19.0%(4/21)、19.0%(4/21)、61.9%(13/21),P=0.007];两两比较显示+8克隆<30%的AA患者明显多于MDS患者(P=0.002),+8克隆≥50%的AA患者明显少于MDS患者(P=0.002).AA与MDS患者中位年龄分别为28(7~61)岁、48.5(16~72)岁,且两者+8克隆负荷与年龄均无显著相关性(rs分别为0.109、-0.022,P值分别为0.528、0.924).异常克隆负荷≥50%定义为大克隆,<50%为小克隆,AA患者大小克隆两组间总铁结合力、转铁蛋白、红细胞生成素差异有统计学意义(P值分别为0.016、0.046及0.012).AA与MDS患者IST有效率分别为66.7%(22/33)、43.8%(7/16)(P=0.215).AA患者治疗后1~2年的+8克隆负荷[45%(5%~85%)]较初诊时[27.3%(4.8%~100.0%)]增加,但差异无统计学意义(z=0.83,P=0.272);MDS患者治疗后1~2年的克隆负荷为70.5%(10%~100%),相比初诊时[72.5%(25%~100%)]略减少.IST后0.5~<1年、1~2年、>2年,AA+8克隆减少组与增加组的IST有效例数无明显变化.AA+8克隆有4种动态演变模式,分别为克隆持续(45%)、克隆消失(30%)、克隆新发(10%)以及克隆反复(15%).结论AA患者+8克隆低负荷,而MDS患者+8克隆高负荷;AA患者的+8克隆在IST后无明显扩增,+8克隆的增减对IST疗效无明显影响.Objective To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure. Methods The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized. Results Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS). Mean size of+8 clone in MDS patients[65%(15%-100%)]was higher than that of AA patients[25%(4.8%-100%), z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6%(20/36);30-50%: 22.2%(8/36);≥50%22.2%(8/36)]and MDS patients[<30%:19.0%(4/21);30%-<50%:19.0%(4/21);≥50%61.9%(13/21)](P=0.007). The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002);and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002). The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (rs=0.109, P=0.125;rs=-0.022, P=0.924, respectively). There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively), but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8%(P=0.125). Comparing with initial clone size (27.3%), the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272). Consistently, there was no significant change between

关 键 词：获得性骨髓衰竭 8号染色三体 克隆演变 免疫抑制治疗 

分 类 号：R551.3[医药卫生—血液循环系统疾病]