伴PNH克隆的骨髓增生异常综合征患者临床和实验室特征分析  

Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones

作　　者：李艳[1] 秦铁军[1] 徐泽锋 张悦 王静雅 李冰 方力维 潘丽娟 胡耐博 张宏丽 曲士强 刘晋琴 王慧君 肖志坚 

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

出　　处：《中华血液学杂志》2016年第4期313-317,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81070403、81530008、81470297）;高等学校博士学科点专项科研基金（20121106130005）

摘　　要：目的分析伴阵发性睡眠性血红蛋白尿症克隆的骨髓增生异常综合征（MDS-PNH）患者的临床特征及PIG-A基因突变等实验室特征。方法回顾性分析2013年8月至2015年8月诊治的218例MDS患者，其中经流式细胞术检出MDS-PNH 13例，选取同期17例再生障碍性贫血（AA）-PNH综合征患者及14例PNH患者，采用直接测序法分析PIG-A基因突变情况，比较各组患者的临床及实验室特征。结果MDS-PNH患者在MDS患者中的比例为5.96%（218例中13例），其中9例MDS-PNH患者使用环孢素A（CsA）治疗，8例获得血液学改善（HI）。MDS-PNH患者粒、红细胞PNH克隆大小及LDH水平[分别为19.2%（1.0%～97.7%）、4.3%（0～67.2%）、246（89～2 014）U/L]与PNH患者[分别为60.2%（3.1%～98.0%）、27.9%（2.5%～83.6%）、1 137（195～2 239）U/L]比较差异均有统计学意义（P值分别为0.026、0.007、0.049），与AA-PNH综合征患者[分别为23.2%（1.5%～96.0%）、14.4%（1.1%～62.8%）、406（192～1 148）U/L]比较差异均无统计学意义（P值均〉0.05）。7例MDS-PNH患者检测到PIG-A基因突变，错义突变6例，移码突变1例，4例患者有相同的突变，为c.356G〉A（R119Q）；9例AA-PNH综合征和11例PNH患者PIG-A基因突变，均存在c.356G〉A（R119Q）。3组患者的PIG-A基因突变均为小克隆突变，以错义突变为主，59%（19/32）的突变发生在2号外显子。结论MDS-PNH患者CsA治疗效果好，PNH克隆较小，基因突变主要集中在2号外显子，可能存在突变热点。Objective To analyze the clinical, laboratory characteristics and PIG-A gene mutations in patients of myelodysplastic syndromes （MDS） with PNH clones. Methods 218 MDS patients diagnosed from August 2013 to August 2015 were analyzed. The PIG-A gene mutations were tested in 13 cases of MDS with PNH clones, 17 cases of AA-PNH and 14 cases of PNH selected contemporaneously by PCR and direct sequencing. Results 13 （5.96%） MDS patients were detected with PNH clones （13/218 cases）. 9 patients were treated with cyclosporin A （CsA）. Patients showed hematological improvement （HI）. There were significant differences between MDS-PNH and PNH patients in terms of granulocyte clone size, red cell clone size and LDH levels [ 19.2% （1.0%-97.7%） vs 60.2%（3.1%-98.0%）,P=-0.007; 4.3%（0-67.2%） vs 27.9%（2.5%-83.6%）, P=0.026; 246（89-2 014） U/L vs 1 137 （195-2 239） U/L, P=0.049], while the differences were not statistically significant in patients between MDS-PNH and AA-PNH patients [ 19.2%（1.0%-97.7%） vs 23.2%（1.5%-96.0%）, P=0.843; 4.3% （0-67.2%） vs 14.4%（1.1%-62.8%）, P=0.079; 246（89-2 014） U/L vs 406（192-1 148） U/L, P=-0.107]. PIG-A gene mutations were detected in 7 MDS-PNH patients, of them, six were missense mutations, one were frameshift mutation and four cases with the same mutation of c.356G〉A （R119Q）. The PIG-A gene mutations were also detected in 9/11 AA-PNH patients and 11/14 PNH patients, both of them had the mutation of c.356G〉A（R119Q）. The PIG-A gene mutations of MDS-PNH, AA-PNH, PNH patients were all small mutations, the majority of those （59%） were missense mutation and mainly located in exon 2. Conclusion MDS patients with PNH clones had better response to CsA, smaller PNH clone size. The PIG-A gene mutations of MDS-PNH patients mainly located in exon 2, which could be a mutational hotspot of these patients.

关 键 词：骨髓增生异常综合征 血红蛋白尿 阵发性 基因 PIG—A 

分 类 号：R551.3[医药卫生—血液循环系统疾病]