PRAME基因在急性白血病中的表达及临床意义分析  

Expression of PRAME Gene in Acute Leukemia and Its Clinical Significance

作　　者：祝毓琳[1] 刘静[1] 朱平[1] 杜金伟[1] 张英[1] 顾江英[1] 

机构地区：[1]北京大学第一医院血液研究室,北京100034

出　　处：《中国实验血液学杂志》2007年第6期1144-1149,共6页Journal of Experimental Hematology

基　　金：国家科技部国际合作重大项目资助(编号2006DFB31430);国家自然科学基金资助(编号30470939)

摘　　要：本研究检测黑色素瘤优先表达抗原(PRAME)基因在不同类型急性白血病(acute leukemia,AL)中的表达及其与病情发展的相互关系。用建立的检测PRAME基因的SYBR Green I荧光实时定量逆转录聚合酶链反应(RQ-RT-PCR)方法,对55例急性白血病患者(急性髓系白血病43例、急性淋巴细胞性白血病9例、其它类型的白血病3例)的骨髓样本进行PRAME基因表达情况的检测。同时选择7例非恶性血液疾病患者的骨髓样本和8例正常人外周血样本作为阴性对照,并用白血病细胞系K562作为阳性对照。结果表明:35例急性白血病患者中检测出不同水平的PRAME基因表达,在其余20例急性白血病患者及15例对照样本中均未检测出PRAME基因,总阳性率64%,两组之间具有非常显著的差异(p<0.005)。在35例PRAME基因阳性表达的患者中,AML28例,阳性检出率为65%,其中以M3、M4和M2亚型的阳性检出率较高,分别为90%、70%、67%;ALL5例,阳性检出率为56%。在31例融合基因阳性患者中,PRAME基因阳性患者为23例,而在24例融合基因阴性患者中,PRAME基因阳性患者达到12例。比较各种临床因素与PRAME表达水平的相关性未发现明显相关。短期观察5例PRAME基因阳性表达的患者显示出经化疗达到完全缓解(CR)后,患者PRAME基因表达均转阴,下降水平为63-23921/106×GAPDH拷贝。长期观察1例M3患者显示化疗后PRAME基因水平逐渐下降并转阴,患者至今仍处于CR状态。结论:PRAME基因在65%的急性白血病中呈阳性表达,其中以M3、M4和M2亚型最常见,在正常个体和非恶性血液病患者中不表达。不同白血病个体之间PRAME基因表达水平不同,随病情缓解其表达水平降低或转阴。PRAME基因可以成为微小残留病(MRD)检测的一种分子标志。This study was aimed to detect the expression levels of preferentially expressed antigen of melanoma （PRAME） gene in acute leukemia （AL） and to evaluate the clinical significance of PRAME gene. The quantitative detection method was established by SYBR Green I real-time quantitative RT-PCR, then PRAME mRNA was measured by this method in 55 cases of acute leukemia, out of which 43 cases were acute myeloid leukemia （ AML）, 9 cases were a- cute lymphocytic leukemia （ALL） and other types leukemia were 3 cases. In addition, expression of PRAME gene was also analyzed in 7 cases of non-malignant hematological diseases and 8 healthy volunteers. K562 cell line was used as a positive control. The results showed that the expression of PRAME gene was found in 35 cases of acute leukemia, the positive percentage was 64%. No expression could be detected in any of the non-malignant hematological diseases and healthy volunteers. In 35 PRAME positive cases, 28 cases were AML, which mainly belonged to M3 , M4 and M2 subtypes, and 5 cases was ALL. In 31 fusion gene positive cases, 23 cases were PRAME positive, and in 24 fusion gene negative cases 12 cases were PRAME positive. No significant relationship was found between PRAME expression level and clinical characteristics （age, sex, WBC count, blast cells in BM）. The expression of PRAME gene decreased or disappeared in 6 patients achieving complete remission （CR）. It is concluded that the PRAME gene expresses in 64% AML patients, which mainly belonged to M3 , M4 and M2 subtypes, no expression could be detected in any of the nonmalignant hematological diseases and healthy volunteers. There is remarkable difference in the level of PRAME transcript of the 35 cases and the expression of PRAME gene decreases or disappeares when the patients achieved complete remission. These results suggest that PRAME expression in acute leukemia may be a useful marker to detect the minimal residual disease （MRD） and to determine the response to therapy in AL patients.

关 键 词：PRAME 急性白血病 基因表达 实时定量逆转录聚合酶链反应 

分 类 号：R733.71[医药卫生—肿瘤] R730.4[医药卫生—临床医学]