【作者】 李曼；

【导师】 顾伟英；

【作者基本信息】 苏州大学 ， 内科学， 2012， 硕士

【摘要】 目的：探讨急性髓系白血病（AML）中hDMP1基因表达特点及其临床意义，并分析其与WT1基因表达水平、NPM1和FLT₃-ITD基因突变的关系。方法：应用实时定量RT-PCR方法检测93例初诊AML患者骨髓细胞hDMP1和WT1基因的表达水平，以β胆色原脱氢酶（GAPDH）表达水平为内参。同时采用DNA测序分析检测NPM1及FLT₃-ITD突变。分析hDMP1基因表达水平与患者临床资料、WT1基因表达水平、NPM1突变和FLT₃-ITD突变关系。结果：93例AML患者骨髓细胞中hDMP1基因中位表达水平476.6（60～2217）较对照组2103（470～3770）显著降低（P=0.002），WT1基因表达水平202.6（49-1134）较正常对照组1.22（0～8.56）显著升高（P=0.001），hDMP1和WT1基因表达水平与患者性别、年龄、有无肝脾淋巴结肿大、起病时外周血WBC计数、骨髓中原始细胞比例、AML亚型、染色体核型分组无关。36例正常核型AML中，8例检测到NPM1阳性突变（22.22%），7例检出FLT₃-ITD突变阳性患者（19.44%）；22例异常核型AML中未检出NPM1基因突变，2例检出FLT₃-ITD突变阳性（5.56%）。NMP1突变组和非突变组hDMP1基因（p=0.15）和WT1基因（p=0.715）表达水平无统计学差异；FLT3-ITD突变组和非突变组hDMP1基因（p=0.692）和WT1基因（p=0.539）表达水平也无统计学差异。结论：急性髓系白血病患者hDMP1基因的低表达伴随WT1基因高表达，两者均参与AML发病。hDMP1基因表达水平与NPM1基因突变和FLT₃-ITD突变无关。更多还原

【Abstract】 Objective To investigate the clinical significance of hDMP1gene expression levelsin acute myeloid leukemias （AMLs） and the correlation between hDMP1and WT1geneexpression, NPM1and FLT₃-ITD gene mutations.Method Real-time quantitative reverse transcriptase polymerase chain reaction（RT-PCR） was applied to detect the hDMP1and WT1gene expression levels in the bonemarrow cells of93newly diagnosed AMLs and13Healthy volunteers, taking GAPDH ashousekeeping gene. DNA sequencing analysis was used to detect NPM1and FLT3-ITDmutation of the same sample simultaneously. The relationship between hDMP1geneexpression level and clinical features, the WT1gene expression level, NPM1mutationsand FLT₃-ITD mutation were further analysed.Results The hDMP1gene expression levels in AML patients were significantly lowerthan those in normal controls （P=0.002）, while WT1gene expression reversely higherin AMLs than in normal controls （P=0.001）. Furthermore both hDMP1and WT1geneexpression levels were of no relevance to sex, age, hepatosplenomegaly, white bloodcell（WBC） count of peripheral blood, the proportion of blasts in bone marrow cells, theFAB subtype of AML or karyotype. Of the36AML cases with normal karyotype, eightwere NPM1mutation-positive （22.22%） and seven cases were FLT₃-ITD mutation-positive（19.44%）. Of the22AML cases with abnormal karyotype, two were FLT3-ITDmutation-positive （5.56%） and no NPM1gene mutation was detected. Both hDMP1gene（p=0.15） and WT1gene （p=0.715） expression levels was of no significant differencebetween NMP1mutation group and non-mutation group; nor between FLT₃-ITD mutationgroup and non-mutation group （p=0.692, p=0.539）. Conclusion hDMP1gene was hypo-expressed in AMLs, while WT1geneover-expressed, indicating both the two genes might participate in the pathogenesis ofacute myeloid leukemia. hDMP1gene expression level were of no relationship with NPM1or FLT₃-ITD gene mutation.更多还原