急性白血病细胞凋亡抑制基因Livin表达及临床意义

急性白血病细胞凋亡抑制基因Livin表

达及临床意义

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【摘要】目的观察Livin 基因在急性白血病(AL)病人白血病细胞中的表达及其临床意义。方法采用半定量逆转录聚合酶链反应(RT PCR)方法检测41例不同时期AL病人白血病细胞Livin mRNA的表达水平，以10例健康人作为正常对照。结果AL病人白血病细胞Livin mRNA 阳性表达率为53.7%。其中急性淋巴细胞白血病(ALL)和急性非淋巴细胞白血病(ANLL)病人Livin mRNA 阳性表达率分别为53.8%、53.6%，二者比较差异无显著性，但均高于正常对照组(10.0%)(P=0.035、0.017)。初治和复发AL病人白血病细胞Livin mRNA 阳性表达率分别为52.4%、85.7%，明显高于对照组(P=0.025、0.004)。缓解组病人Livin mRNA阳性表达率为15.4%，明显低于初治组和复发组(P=0.004、0.030)，而与对照组相比差异无统计学意义。白细胞计数≥50×109/L的初治白血病病人Livin mRNA 的阳性表达率(77.8%，7/9)明显高于白细胞计数50×109/L的初治病人(25.0%，3/12)(P=0.022)，其表达水平也明显高于后者(T=6.50，

P0.05)。结论Livin mRNA过度表达参与了AL的发病，可作为AL 的诊断、复发及预后判断的指标之一。Livin mRNA表达在AL细胞的增殖分化和(或) 抗凋亡过程中发挥了重要作用，可能是导致AL细胞对化疗药物不敏感的原因之一，可作为治疗的一个潜在靶点。

【关键词】Livin 基因;白血病;逆转录聚合酶链反应

[ABSTRACT] Objective To explore the correlation between the expression of Livin gene in acute leukemic (AL) cells and its clinical significance. Methods The levels of leukemic cell Livin mRNA in 41 AL patients and 10 healthy controls were measured by semi quantitative reverse transcriptase polymerase chain reaction (RT PCR) technique. Results The positive expression rate of leukemic cell Livin mRNA in the patients was 53.7%, and that of Livin mRNA in ALL cells and ANLL cells were 53.8% and 53.6%, respectively, the difference between them was not significant, but higher than that in normal controls (10.0%) (P=0.035,0.017). The expression of Livin mRNA in initially treated AL patients and the recurrent was 52.4% and 85.7%, respectively, which was significantly higher than that in normal controls (P=0.025,0.004). The expression of Livin mRNA in patients at remission was 15.4%, which was lower than that in initially treated and recurrent patients (P=0.004,0.030), but there was no statistical significance as compared with normal controls. Besides, the initially treated AL

patients with a leukocyte count of at least 50×109 /L had a significantly higher Livin mRNA expression rate (77.8%,7/9) than that with a leukocyte count of less than 50×109 /L (25.0%,3/12) (P=0.022). In addition, the level of Livin mRNA in the former was significantly higher than that of the latter (T=6.50,P0.05). Conclusion Overexpression of Livin mRNA involves in the pathogenesis of acute leukemia, which can be used as one of the parameters in the diagnosis, prediction of recurrence and prognosis of the disease. The expression of Livin mRNA plays an important effect on the proliferation and differentiation of AL cells, which may be one of the reasons leading to insensitive to chemotherapy of AL cells and be used as a potential target for the treatment of the disease.

[KEY WORDS] Livin gene; leukemia; reverse transcriptase polymerase chain reaction

凋亡抑制是肿瘤细胞的一个普遍特性。近年发现的凋亡蛋白抑制因子(IAP)是一类重要的抗细胞凋亡因子，与肿瘤的发生发展关系密切。目前，人类IAPs家族中已发现有NIAP、XIAP、clAP1、clAP2、survivin、apollon、ILP2和Livin共8个成员，其抗凋亡功能远强于Bc12家族，在肿瘤的发病机制中起着重要作用。其中clAP1、clAP2、survivin等多个IAP家族成员在白血病细胞中高表达，且与预后相关[13]。Livin是IAPs家族中的一个新成员，有2种异构体(Livin