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作 者:周培一[1] 李维佳[1] 魏彩霞[1] 周挚[1]
机构地区:[1]昆明医学院第一附属医院血液科,昆明650031
出 处:《中国实验血液学杂志》2007年第6期1177-1181,共5页Journal of Experimental Hematology
基 金:云南省教育厅科学研究基金重点资助项目;编号04Z022C
摘 要:本研究探讨黑色素瘤特异性抗原(preferentially expressed antigen of melanoma,PRAME)基因在成人急性白血病中的表达及其与预后的相关性。应用逆转录-聚合酶链反应(RT-PCR)技术检测73例初发、3例复发成人急性白血病患者、7例特发性血小板减少性紫癜(ITP)患者和8例正常人骨髓单个核细胞(BMMNC)以及K562和U937二个白血病细胞株PRAME mRNA的表达水平,分析其在成人急性白血病中的表达规律及其在判断疗效及预后、监测微小残留病(MRD)和在特异性免疫治疗中的意义。结果表明:PRAME基因在成人急性白血病中的表达率为36.8%(n=28),急性髓系白血病(AML)为42.9%(n=24),急性淋巴细胞白血病(ALL)为20%(n=4)。AML的表达率显著高于ALL(P<0.01)。在K562和U937细胞都有PRAME基因表达,它们的表达水平分别为0.57和0.46。在15例对照(正常人、ITP患者)未检出PRAME基因表达。AML各亚型之间(除去病例数为0例的M7,M1及M6各1例)、ALL各亚型(L1,L2)之间PRAME mRNA的表达水平无显著性差异。患者的年龄、初诊或者复发时白细胞计数、血红蛋白、血小板计数、骨髓中原始细胞、幼稚细胞比例以及脾脏厚度对PRAME mRNA的表达无相关性。完全缓解组PRAME mRNA的表达水平与部分缓解组和死亡组有显著性差异,并且随着PRAME mRNA的表达水平升高,治疗效果越好。对1例病人动态监测发现,在复发之前PRAME mRNA的表达会升高。结论:PRAME基因在成人急性白血病中存在高表达,其表达水平与预后密切相关,并可以作为监测MRD的标志基因。PRAME在白血病特异性免疫治疗中是潜在的靶抗原。The study was aimed to investigate the expression of preferentially expressed antigen of melanoma (PRAME) gene in adult acute leukemia and its clinical significance. The expression of the PRAME gene of bone marrow was measured by reverse transcriptase polymerase chain reaction (RT-PCR) in 73 adult newly diagnosed acute leukemia patients, 3 relapsed patients, 7 patients with idiopathic thrombocytopenic purpura (ITP) and 8 healthy donors , as well as two AL cell-lines ( K562 and U937 ). The results indicated that PRAME mRNA was expressed in 42.9% AML patients (n = 24 ) and 20% ALL patients (n = 4 ), also in two leukemia cell-lines K562 and U937, but not in eight health donors and seven ITP patients. PRAME expression not correlated to the white blood count, hemoglobin level, platelet count and the percentage of blasts at diagnosis, yet independent of age, sex, and FAB type. PRAME mRNA expression in complete remission group seems much higher than those in partial complete remission group and death group. The increased levels of expression could be found prior to the relapse in one patient being regularly monitored. PRAME gene was overexpressed in adult acute leukemia patients and leukemia cell-lines. It is concluded that the expression of PRAME is an indicator of favorable prognosis and can be a useful tool for monitoring minimal residual disease (MRD) in adult acute leukemia. Differential expression between adult acute leukemia patients and healthy volunteers suggests that the immunogenic antigens PRAME are potential candidates for immunotherapy in adult acute leukemia.
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