EVI1在急性髓系白血病和急性淋系白血病中的表达及其临床意义
发布时间：2018-01-01 09:23
本文关键词：EVI1在急性髓系白血病和急性淋系白血病中的表达及其临床意义 出处：《苏州大学》2015年硕士论文 论文类型：学位论文
【摘要】：【目的】研究EVI1在中国AML和ALL患者中的表达及其临床意义。【方法】收集2006至2011年间苏州大学附属第一医院就诊的263例AML患者和70例ALL患者的骨髓,就诊时患者年龄均小于80岁,另外收集13例正常人捐献的骨髓作为正常对照。Ficoll法分离骨髓样本中的单个核细胞,提取总RNA,实时荧光定量RT-PCR检测EVI1 m RNA的相对表达水平,比较AML,ALL患者与正常对照之间EVI1 m RNA的表达差异。通过统计学方法分析EVI1 m RNA表达与患者白血病分型,年龄,性别,细胞核型,白细胞计数,血小板计数,骨髓原幼细胞(%),NRAS突变,DNMT3A突变,FLT3-ITD突变,预后等临床特征之间的相关性。【结果】1.AML和ALL患者较正常对照都有较高的EVI1 m RNA表达水平(P0.01),而AML和ALL之间比较没有显著差异(P0.05);进一步分析,与正常对照比较,AML各亚型中,M0和M6患者低表达EVI1(P0.001),M1,M2及M5患者高表达EVI1(P0.05),而ALL中,B-ALL和T-ALL都高表达EVI1(P0.05)。2.EVI1 m RNA过表达患者占AML总人数的10.3%,占ALL总人数的20.0%,两者比较有显著差异(P=0.01),而EVI1低表达患者占AML总人数的38.7%,占ALL总人数的52.9%,两者比较有显著差异(P=0.01);AML-M3过表达EVI1患者有11例占25.0%,与其他组比较有显著差异(P=0.001),而AML-M0有10例患者低表达EVI1占100%,AML-M4有18例患者低表达EVI1占64.3%,AML-M6有13例患者低表达EVI1占93.4%,与其他组比较均有显著差异(P0.05)。3.细胞核型分析,发现AML中核型异常患者较核型正常患者有更高的EVI1m RNA表达水平(P=0.001),而ALL中却没有显著差异;t(8;21),inv(16)和+8核型患者相比正常对照有较低的EVI1表达水平(P0.05);t(9;22)核型阳性的B-ALL患者较非t(9;22)B-ALL阳性患者有更低的EVI1表达水平。4.发现EVI1 m RNA表达与人类白细胞分化抗原表达之间的关系:AML中,EVI1表达与HLA-DR,CD7,CD34表达负相关(Spearman检验,P0.05),而与CD15表达正相关(Pearson检验,P0.001);ALL中,EVI1表达与CD14表达负相关(Spearman检验,P=0.012),而与CD10表达正相关(Spearman检验,P=0.007)。5.通过分析EVI1 m RNA表达与其他临床特征之间的关系,还发现:AML中,女性患者有较高比例的EVI1过表达患者(P=0.019);而大于60岁的AML患者相比正常对照有较低的EVI1表达水平(P0.001);AML-M1和T-ALL患者EVI1表达水平与PLT正相关(Spearman检验,P0.05),而AML-M3患者EVI1表达水平与Blasts(%)有显著负相关(Pearson检验,P0.001);低表达EVI1的AML患者有更高比例的FLT3-ITD突变(P=0.012)。6.分析EVI1表达对AML和ALL患者预后的影响,发现:AML中,单因素分析,高表达EVI1 m RNA患者有较差的预后(P=0.038,HR=1.648),而多因素分析时,高表达EVI1患者也有较差的预后(P=0.009,HR=2.019),表明EVI1高表达在AML中是一个独立的危险预后因子,另外,还发现EVI1高表达的AML-M3患者也具有极显著的不良预后(Long-Rank检验,P=0.003);但是,分析EVI1高表达在ALL中的预后意义,并没有发现显著差异。【结论】综上所述,EVI1 m RNA在AML和ALL中的表达具有显著差异。AML-M1和AML-M6显著低表达EVI1,AML-M3过表达EVI1,B-ALL和T-ALL之间没有显著差异;t(8;21),inv16和+8核型患者低表达EVI1,B-ALL中t(9;22)核型阳性患者低表达EVI1;低表达EVI1的AML患者具有较高的FLT3-ITD突变比例;AML-M3患者EVI1 m RNA表达水平与Blasts(%)负相关,而AML-M1和T-ALL患者的EVI1 m RNA表达水平与PLT正相关;AML患者EVI1 m RNA表达水平与人类白细胞分化抗原HLA-DR,CD7,CD34表达负相关,与CD15表达正相关,而ALL患者EVI1 m RNA表达水平与人类白细胞分化抗原CD14表达负相关,与CD10表达正相关;高表达EVI1m RNA在AML中是一个独立的不良预后因子,且在AML-M3中也显示预后不良,而在ALL中高表达EVI1预后意义并不明显。本研究发现了EVI1表达在中国急性白血病患者中的一些新的临床意义,有助于理解EVI1在急性白血病中的病理作用。
[Abstract]:[Objective] to study the expression and clinical significance of EVI1 in China AML and ALL patients. [method] 263 cases of AML were collected from 2006 to 2011 years in First Hospital Affiliated to Suzhou University for treatment of 70 patients with ALL and bone marrow treatment when patients age less than 80 years old, also collected 13 cases of normal bone marrow donors as normal control by.Ficoll isolation of mononuclear cells in bone marrow samples, extracted the total RNA, compared the relative expression level of EVI1 m RNA, detected by real-time fluorescence quantitative RT-PCR AML expression difference between ALL patients and normal control EVI1 m RNA. The expression and analysis of leukemia patients with type EVI1 M RNA through the statistical method of age, gender, karyotype, white cell count, platelet count, bone marrow blasts (%), NRAS mutation, DNMT3A mutation, FLT3-ITD mutation, the correlation between clinical features and prognosis. [result] 1.AML and ALL patients compared with normal to 鐓ч兘鏈夎緝楂樼殑EVI1 m RNA琛ㄨ揪姘村钩(P0.01),鑰孉ML鍜孉LL涔嬮棿姣旇緝娌℃湁鏄捐憲宸紓(P0.05);杩涗竴姝ュ垎鏋，
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