EVI1在急性髓系白血病和急性淋系白血病中的表達及其臨床意義
發(fā)布時間:2018-01-01 09:23
本文關鍵詞:EVI1在急性髓系白血病和急性淋系白血病中的表達及其臨床意義 出處:《蘇州大學》2015年碩士論文 論文類型:學位論文
【摘要】:【目的】研究EVI1在中國AML和ALL患者中的表達及其臨床意義。【方法】收集2006至2011年間蘇州大學附屬第一醫(yī)院就診的263例AML患者和70例ALL患者的骨髓,就診時患者年齡均小于80歲,另外收集13例正常人捐獻的骨髓作為正常對照。Ficoll法分離骨髓樣本中的單個核細胞,提取總RNA,實時熒光定量RT-PCR檢測EVI1 m RNA的相對表達水平,比較AML,ALL患者與正常對照之間EVI1 m RNA的表達差異。通過統(tǒng)計學方法分析EVI1 m RNA表達與患者白血病分型,年齡,性別,細胞核型,白細胞計數(shù),血小板計數(shù),骨髓原幼細胞(%),NRAS突變,DNMT3A突變,FLT3-ITD突變,預后等臨床特征之間的相關性。【結(jié)果】1.AML和ALL患者較正常對照都有較高的EVI1 m RNA表達水平(P0.01),而AML和ALL之間比較沒有顯著差異(P0.05);進一步分析,與正常對照比較,AML各亞型中,M0和M6患者低表達EVI1(P0.001),M1,M2及M5患者高表達EVI1(P0.05),而ALL中,B-ALL和T-ALL都高表達EVI1(P0.05)。2.EVI1 m RNA過表達患者占AML總?cè)藬?shù)的10.3%,占ALL總?cè)藬?shù)的20.0%,兩者比較有顯著差異(P=0.01),而EVI1低表達患者占AML總?cè)藬?shù)的38.7%,占ALL總?cè)藬?shù)的52.9%,兩者比較有顯著差異(P=0.01);AML-M3過表達EVI1患者有11例占25.0%,與其他組比較有顯著差異(P=0.001),而AML-M0有10例患者低表達EVI1占100%,AML-M4有18例患者低表達EVI1占64.3%,AML-M6有13例患者低表達EVI1占93.4%,與其他組比較均有顯著差異(P0.05)。3.細胞核型分析,發(fā)現(xiàn)AML中核型異;颊咻^核型正常患者有更高的EVI1m RNA表達水平(P=0.001),而ALL中卻沒有顯著差異;t(8;21),inv(16)和+8核型患者相比正常對照有較低的EVI1表達水平(P0.05);t(9;22)核型陽性的B-ALL患者較非t(9;22)B-ALL陽性患者有更低的EVI1表達水平。4.發(fā)現(xiàn)EVI1 m RNA表達與人類白細胞分化抗原表達之間的關系:AML中,EVI1表達與HLA-DR,CD7,CD34表達負相關(Spearman檢驗,P0.05),而與CD15表達正相關(Pearson檢驗,P0.001);ALL中,EVI1表達與CD14表達負相關(Spearman檢驗,P=0.012),而與CD10表達正相關(Spearman檢驗,P=0.007)。5.通過分析EVI1 m RNA表達與其他臨床特征之間的關系,還發(fā)現(xiàn):AML中,女性患者有較高比例的EVI1過表達患者(P=0.019);而大于60歲的AML患者相比正常對照有較低的EVI1表達水平(P0.001);AML-M1和T-ALL患者EVI1表達水平與PLT正相關(Spearman檢驗,P0.05),而AML-M3患者EVI1表達水平與Blasts(%)有顯著負相關(Pearson檢驗,P0.001);低表達EVI1的AML患者有更高比例的FLT3-ITD突變(P=0.012)。6.分析EVI1表達對AML和ALL患者預后的影響,發(fā)現(xiàn):AML中,單因素分析,高表達EVI1 m RNA患者有較差的預后(P=0.038,HR=1.648),而多因素分析時,高表達EVI1患者也有較差的預后(P=0.009,HR=2.019),表明EVI1高表達在AML中是一個獨立的危險預后因子,另外,還發(fā)現(xiàn)EVI1高表達的AML-M3患者也具有極顯著的不良預后(Long-Rank檢驗,P=0.003);但是,分析EVI1高表達在ALL中的預后意義,并沒有發(fā)現(xiàn)顯著差異!窘Y(jié)論】綜上所述,EVI1 m RNA在AML和ALL中的表達具有顯著差異。AML-M1和AML-M6顯著低表達EVI1,AML-M3過表達EVI1,B-ALL和T-ALL之間沒有顯著差異;t(8;21),inv16和+8核型患者低表達EVI1,B-ALL中t(9;22)核型陽性患者低表達EVI1;低表達EVI1的AML患者具有較高的FLT3-ITD突變比例;AML-M3患者EVI1 m RNA表達水平與Blasts(%)負相關,而AML-M1和T-ALL患者的EVI1 m RNA表達水平與PLT正相關;AML患者EVI1 m RNA表達水平與人類白細胞分化抗原HLA-DR,CD7,CD34表達負相關,與CD15表達正相關,而ALL患者EVI1 m RNA表達水平與人類白細胞分化抗原CD14表達負相關,與CD10表達正相關;高表達EVI1m RNA在AML中是一個獨立的不良預后因子,且在AML-M3中也顯示預后不良,而在ALL中高表達EVI1預后意義并不明顯。本研究發(fā)現(xiàn)了EVI1表達在中國急性白血病患者中的一些新的臨床意義,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揪姘村鉤(P0.01),鑰孉ML鍜孉LL涔嬮棿姣旇緝娌℃湁鏄捐憲宸紓(P0.05);榪涗竴姝ュ垎鏋,
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