Aurora家族基因在急性白血病细胞中的表达及其临床意义

摘要

目的:研究Aurora-A、B、C(AUR-A、B、C)基因mRNA在急性白血病中的表达情况及其与临床指标的相关性.方法:采用荧光定量PCR检测73例初诊急性白血病(AL)患者(初诊组)、20例化疗完全缓解急性白血病患者(缓解组)和骨髓单个核细胞中AUR-A、B、C mRNA表达水平,14例健康志愿者作为对照(健康组),并分析它们分别在不同分组中的表达性差异,与临床指标的相关性及AUR-A、B、CmRNA表达水平之间的相关性.结果:AUR-A、B、C mRNA表达在初诊组均高于健康组和缓解组(P＜0.01),健康组和缓解组3种基因mRNA表达水平差异均无统计学意义(P＞0.05),AUR-A、B、C3种基因mRNA表达水平在急性淋巴细胞白血病(ALL)组均高于急性髓系白血病(AML)组(P ＜0.01);AUR-A、B、C mRNA表达在高危组均高于低危组(P＜0.05),在高危组与中危组及中危组与低危组之间差异无统计学意义(P ＞0.05);AUR-A、B、C表达在CD34、CD71、CD56阴性组和阳性组差异无统计学意义(P＞0.05),在不同性别、染色体、1疗程化疗是否缓解分组中差异无统计学意义(P＞0.05).73例初诊AL患者中,AUR-A mRNA表达水平与初诊乳酸脱氢酶(LDH)水平和危险分层呈显著正相关(r=0.279,P=0.017;r=0.314,P=0.007);AUR-B与初诊LDH水平和危险分层呈显著正相关(r=0.277,P=0.018;r=0.349,P=0.002),AUR-A、B均与年龄、初诊白细胞(WBC)水平、初诊骨髓幼稚细胞比例和1疗程是否缓解无显著相关性;AUR-C表达水平与初诊白细胞水平、初诊LDH水平和危险分层显著正相关(r=0.263,P=0.025;r=0.348,P=0.003;r=0.376,P=0.001),与年龄显著负相关(r=-0.241,P=0.040),而与初诊骨髓中幼稚细胞比例和1疗程是否缓解无显著相关性;AUR-A和B(r =0.444,P=0.000)、AUR-B和C(r=0.763,P=0.000)、AUR-A和C(r=0.616,P=0.000) mRNA表达水平均呈显著正相关.结论:AUR-A、B、C mRNA在初诊急性白血病患者中高表达并且三者间表达水平显著正相关,其高表达与白血病类型、危险分层、初诊白细胞和乳酸脱氢酶水平等指标相关,均可作为预后指标和潜在治疗靶点.%Objective:To explore the mRNA expression of Aurora-A,B,C(AUR-A,B,C) in acute leukemia(AL) and their correlations with the clinical indications.Methods:The mRNA expression levels of A UR-A,B,C in 73 cases of newly diagnosed AL (untreated group),20 cases of AL with remission (remission group) and 14 healthy volunteers as control (healthy group) were detected by QRT-PCR,and the difference of expression levels in difference groups,their correlations with clinical indicators and the correlation between the AUR-A,B,C mRNA expression levels themselves were analyzed.Results:The mRNA expression levels of AUR-A,B,C in untreated group were all higher than those in healthy group and remission group (P ＜ 0.01),but there was not significant difference between healthy group and remission group(P ＞ 0.05);the mRNA expressions of AUR-A,B,C in acute lymphoblastic leukemia(ALL) group were all significantly higher than that in AML group(P ＜ 0.01).The mRNA expression of AUR-A,B,C in high risk group was higher than that in low risk group(P ＜ 0.05),but there was no difference in mRNA expression of A UR-A,B,C between high risk group and middle risk group as well as between middle risk group and low risk group (P ＞ 0.05).The mRNA expression of AUR-A,B,C in CD34,CD71 and CD56 negative group was not statistically different from that in CD34,CD71 and CD56 positive group(P ＞ 0.05).In 73 cases of newly diagnosed AL,the mRNA expression levels of AUR-A,B significantly were positively correlated with lactate dehydrogenase(LDH) level and risk stratificaton (r =0.279,P=0.017;r=0.314,P =0.007 and r =0.277,P =0.018;r =0.349,P =0.002),while the mRNA expression levels of AUR-A,B were not significantly correlated with age,WBC count,blast ratio in bone marrow at initial diagnosis and remission or no-remission after 1 cours of chemotherapy;the mRNA expression level of AUR-C was significantly positively correlated with WBC count (r =0.263,P--0.025),and LDH level (r =0.348,P =0.003) at initial diagnosis and risk stratificantion(r =0.376,P =0.001),and negatively correlated with age (r =-0.241,P =0.040),and was not significantly correlated with blast ratio in bone marrow at initial diagnosis and remission or noremission after 1 course of chemotherapy.There were significant positive correlations in the mRNA expression between AUR-A and B (r =0.444,P =0.000),AUR-B and C (r =0.763,P =0.000) as well as AUR-A and C (r =0.616,P =0.000).Conclusion:Aur-A,B,C mRNA were highly expressed in patients with newly diagnosed AL,moreover the mRNA expression levels of Aur-A,B,C were positively correlated with each other,the high expression of Aur-A,B,C are associated with leukemia types,risk stratification,WBC count and LDH level at initial diagnosis,so they all maybe used as the prognostic markers and potential therapeutic targets.