细胞周期蛋白A在成人急性白血病中的表达及意义

Expression of cyclin A in adult patients with acute leukemia

目的 探讨细胞周期蛋白A(cyclinA)在成人急性白血病 (AL)患者骨髓细胞中的表达及其临床意义。方法 采用RT PCR法对 10 0例初治及复发的AL患者进行cyclinAmRNA水平的检测 ,对其阳性表达的PCR扩增产物进行DNA测序分析。对其中 75例AL患者 ,用流式细胞术检测cyclinA蛋白表达水平 ,10例正常人作为对照。 结果 (1)AL患者cyclinA蛋白表达在细胞周期中的分布无异常 ,cyclinA蛋白及mRNA的阳性率 (分别为 6 6 7% ,5 9 0 % )和中位表达水平 (分别为18 5 % ,0 5 39± 0 4 90 )明显高于正常人 ,同一实验条件下未发现在正常人中有cyclinA蛋白及mRNA阳性表达 (P <0 0 1) ;经测序分析发现cyclinA阳性扩增片段序列与基因库中的目标序列完全一致 ;(2 )cyclinA蛋白及mRNA水平与S期、G2 /M期细胞所占的比例呈正相关 (P <0 0 1)。 (3)复发组急性淋巴细胞性白血病 (ALL)患者的cyclinA蛋白表达水平 (15 4 % )明显低于初治组(2 9 5 % ) ,差异有统计学意义 (t=14 4 18,P =0 0 2 2 )。 (4 )cyclinA蛋白或mRNA高表达患者的完全缓解率 (分别为 87 9%、85 7% )明显高于低表达患者 (分别为 38 2 %、5 3 3% ) (P <0 0 5 )。结论 cyclinA在AL患者中是一种增殖标志 ,是影响AL患者完全缓解率的因素 ,其高表达可能是AL患者?

Objective To investigate the clinical significance of cyclin A expression in adult patients with acute leukemia (AL). Methods 4 ml bone marrow was extracted from 100 AL patients and 10 normal controls to isolate the mononuclear cells (MNCs). The cyclin A mRNA levels in these MNCs were measured by RT-PCR. The cyclin A protein level and cell cycle in 75 randomly selected AL patients and 10 normal controls were examined by flow cytometric analysis. Results (1)The distribution of cyclin A protein was normal in cell cycle in AL patients. The positive rates of cyclin A protein and mRNA were 66.7% and 59%, significantly higher than those in the normal controls (0 and 1.4% respectively, both P <0.01). The median expression levels of cyclin A protein and mRNA of cyclin A in AL patients were 18.5% and 0.539±0.490 respectively, significantly higher than those in the normal controls (both P <0.01). Sequence analysis showed a complete consistency between the positive segment of cyclin A and the objective gene in GeneBank. (2) The levels of cyclin A protein and mRNA were positively correlated with the cumulative percentages of cells in S and G 2/M phases ( P <0.01). (3) The expression level of cyclin A protein in the recurrent acute lymphoblastic leukemia (ALL) group was 15.4%, significantly lower than those of de novo group (29.5%, t =14.418, P =0.022). (4) The complete remission (CR) rates in the AL patients with high expression levels of cyclin A protein and mRNA group were 87.9% and 85.7% respectively, significantly higher than those in the AL patients with low expression levels (38.2% and 53.5% respectively, both P <0.01). Multivariate regression analysis showed that cyclin A was one of the influencing factors of CR rate of AL patients ( P <0.05). Conclusion Cyclin A expression contributes to the high proliferative activity in leukemia cells. The abnormal expression of cyclin A might be a prognostic marker of CR rate in AL patients.