成年人T细胞性急性淋巴细胞白血病磷酸酶及张力蛋白同源基因突变特点和临床意义  

Characteristics and clinical significance of phosphatase and tensin homolog mutations in adult T-cell acute lymphoblastie leukemia

作　　者：韩旗[1] 顾岩 高雨乔 李建勇[1] 陈宝安[2] 葛峥[1,2] Hart Qi1, Gu Yan2, Gao Yuqiao2, Li Jianyong1, Chert Baoan2, Ge Zheng1,2(1.Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China ; 2.Department of Hematology, Zhongda Hospital, Southeast University Medical School, Nanjing 210009, China)

机构地区：[1]南京医科大学第一附属医院江苏省人民医院血液科,210029 [2]东南大学附属中大医院血液科,南京210009

出　　处：《白血病．淋巴瘤》2018年第4期216-221,共6页Journal of Leukemia & Lymphoma

基　　金：国家自然科学基金面上项目（81770172、81270613）;江苏省重点研发项目（BE2017747）;美国米尔斯坦亚美医学基金（2017）

摘　　要：目的探讨成年人T细胞性急性淋巴细胞白血病（T-ALL）中磷酸酶及张力蛋白同源基因（PTEN）突变特点及其与预后的关系。方法选择2010年2月至2016年4月在江苏省人民医院就诊的成年T-ALL患者55例，采用Fieoll密度梯度离心法提取骨髓单个核细胞，从分离出来的单个核细胞中提取基因组DNA，聚合酶链反应（PCR）特异性扩增PTEN外显子，DNA纯化，测序，比对，分析突变发生率、突变类型及其与各临床指标的关系。结果55例成年T-ALL患者中，5例检测出PTEN突变，共检测到8种突变类型，均位于外显子7，突变发生率为9．1％（5／55）。PTEN突变的5例患者均合并有NOTCH1、DNM2等其他基因的突变。PTEN突变组患者中位乳酸脱氢酶（LDH）水平高于非突变组（3358U／L比755U／L），差异有统计学意义（Z=-2．014，P=0．044）；两组患者性别、年龄、白细胞计数、血红蛋白、血小板计数、总生存率、无事件生存率、无复发生存率差异均无统计学意义（均P〉0．05）。结论PTEN作为一种重要的肿瘤抑制基因，其突变在成年人T-ALL的发生发展中起重要作用，可能与预后不良有关。Objective To detect the characteristics of phosphatase and tensin homolog （PTEN） mutations in adult T-cell acute lymphoblastie leukemia （T-ALL） and its relationship with the prognosis. Methods Fifty-five adult T-ALL patients were enrolled in Jiangsu Province Hospital from February 2010 to April 2016. Mononuclear bone marrow cells were extracted by using Ficoll density gradient eentrifugation. Genomic DNA was extracted from isolated mononuclear cells. Amplified exon 1-9 of PTEN by polymerase chain reaction （PCR） specifically amplified PTEN exon, then DNA was purified, sequenced and compared. The mutation occurrence rate, mutation types, and the relations with several clinical indicators were analyzed. Results PTEN mutations were detected in 5 patients, and 8 types of mutations were detected in 55 T-ALL patients with mutation rate of 9.1% （5/55）. All the mutations were located in exon 7 of the genes. Five patients with PTEN mutations also merged other gene mutations like NOTCH1 and DNM2. The level of median lactate dehydrogenase （LDH） in patients with PTEN mutations was higher than that in patients without PTEN mutations （3 358 U/L vs. 755 U/L, Z = -2.014, P = 0.044）. No significant differences were found in gender, age, white blood count, hemoglobin, platelet count, overall survival rate, event free survival, recurrence free survival between the two groups （P 〉 0.05）. Conclusion PTEN is a tumor suppressor gene,and its mutation plays a significant role in the occurrence and development of adult T-ALL patients, which may be associated with the poor prognosis.

关 键 词：白血病 T细胞 急性 PTEN突变 预后 

分 类 号：R733.71[医药卫生—肿瘤]