PRAME基因在血液恶性肿瘤中的表达及相关研究

目的:研究PRAME基因在慢性粒细胞白血病、淋巴瘤和多发性骨髓瘤中的表达及临床意义,探讨PRAME基因在血液恶性肿瘤微小残留病(MRD)监测中的意义。方法:应用半定量逆转录-聚合酶链反应(RT-PCR)技术,检测76例血液肿瘤病人,其中36例慢性粒细胞白血病(CML)、20例淋巴瘤(NHL18例,HD2例)、20例多发性骨髓瘤(MM),10例正常人骨髓单个核细胞(BMMNC)以及K562细胞株PRAME mRNA的表达水平;同时检测CML患者BCR/ABL融合基因的表达并与PRAME的表达结果相比较。结果:10例正常人骨髓PRAME基因表达均呈阴性。PRAME在慢性粒细胞白血病中的表达率为22.2%(n=8),慢粒慢性期(CML-CP)表达阴性,慢粒加速期(CML-AP)表达率为16.7%(n=1),慢粒急变期(CML-BC)表达率为46.7%(n=7),慢粒急变期的表达率显著高于慢性期和加速期(P<0.05)。36例CML患者BCR/ABL融合基因表达率为97.2%(n=35),与PRAME基因表达无相关性(Fisher精确概率法,P>0.05)。3例经历了慢性期、加速期和急变期的CML患者均在急变期检测到PRAME基因的表达。淋巴瘤中PRAME表达率为10%(n=2),其中2例阳性均为弥漫大B细胞淋巴瘤。PRAME在多发性骨髓瘤中的表达率为20%(n=4),其中4例阳性均是在MMⅢ期(28.6%),与I、II期的表达无明显差异(P>0.05)。PRAME mRNA表达水平与性别、年龄、初诊或复发时白细胞计数、血红蛋白、血小板计数、骨髓中原幼细胞比例无明显相关性(P>0.05)。结论:PRAME基因在多种血液恶性肿瘤中表达,与慢性粒细胞白血病病情进展密切相关,与CML患者BCR/ABL基因的表达无相关性,可作为PRAME阳性血液恶性肿瘤MRD监测的标志基因。

Objective To determine clinical significance of PRAME gene in CML,lymphoma and MM and its implications for monitoring minimal residual disease in haematological malignancy. Methods The expression of PRAME mRNA was detected in 36 CML,20 lymphoma,20 MM,10 normal subjects and one AL cell-line(K562) by using semi-quantitative RT-PCR and compared with the expression of BCR/ABL in 36 CML. Results PRAME mRNA was negative in bone marrow cells from 10 normal subjects. PRAME gene was expressed in 22.2%(n=8)CML patients,of which,16.7%(n=1) CML-AP patients and 46.7%(n=7)CML-BC patients,but PRAME gene in CML-CP was all negative. The expression of PRAME had significant difference between CML-CP,CML- AP and CML-BC(P<0.05). BCR/ABL gene was revealed in 35 of 36 CML patients(97.2%) and its expression had no correlation with PRAME gene(P>0.05). Only 2 NHL were detected the expression of PRAME gene. It had no significant difference with normal group(P>0.05). In addition,We analyzed 20 bone marrow samples from patients with MM for the expression of PRAME gene. PRAME gene in all of the samples of patients with stage I and stage II myeloma were found negative,4 PRAME-positive patients were in stage III(28.6%). PRAME expression was not correlated to the white blood count,hemoglobin,platelet count and the percentage of blasts,also independent of age and gender. Conclusions PRAME gene expressed in several haematological malignancy. Its expression was correlated to stages of CML while had no correlation with BCR/ABL gene. It could be a useful tool for monitoring minimal residual disease in haematological malignancy with PRAME positive.