Cyclin B1 and p21^(cipl)在急性白血病中的表达及其相关性研究(英文)

Expressions of Cyclin B1 and p21^(cipl) in Adult Acute Leukemia and Their Correlation

细胞周期蛋白(cyclin)B1作为调节细胞进行有丝分裂的正性调节因子,在细胞增殖中起到重要作用。本研究旨在评价cyclinB1在急性白血病(AL)发生、发展中的作用及其对AL患者预后判断的价值。采用流式细胞术对136例初治AL成人患者、10例持续完全缓解(CCR)患者及17例正常人进行cyclinB1、p21cipl蛋白表达水平检测和细胞周期分布分析;采用RTPCR测定CyclinB1、p21cipl和增殖细胞核抗原(PCNA)mRNA水平。结果显示:136例初治AL患者cyclinB1蛋白表达水平明显高于正常对照组;复发AL患者的cyclinB1表达水平明显高于正常对照组,但低于初治AL患者;缓解AL患者及CCR的AL患者cyclinB1蛋白表达水平与正常对照比较均无显著性差异;所有cyclinB1高表达的AL患者出现非顺序表达(cyclinB1在G1期出现,有些甚至G2期高表达),cyclinB1与p21cipl的蛋白表达呈负相关;cyclinB1蛋白表达与其mRNA水平呈正相关;cyclinB1表达与PCNA及细胞增殖指数(PI)表达水平呈正相关;cyclinB1表达水平高的AL患者有较高的缓解率和生存率,但有较高的复发率。结论:本研究首次发现cyclinB1在成人AL患者有过度表达和异常分布,认为cyclinB1与AL发生、发展有关,是影响AL患者预后的因素之一。

Cyclin B1, a positive regulator, controls mitosis occurrence, plays an important role in cell proliferation.To investigate the clinical significance of cyclin B1, the expression of cyclin B1 in acute leukemia （AL） patients was measured; the expression of cyclin B1 and p21^cipl, and their cell cycle distribution were assayed by flow cytometry in 136 adult patients with newly diagnosed AL, 10 continuous complete remission （CCR） AL and 17 normal controls; the mRNA of cyclin B 1 and p21^cipl, and the proliferation cell nuclear antigen （PCNA） in patients and normal controls were detected with semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. The results showed that the expression of cyclin B1 in newly diagonsed AL patients was significantly higher than that in normal controls. For the relapsed AL patients, the cyclin B1 expression was also higher than that in normal controls, but lower than that in newly diagnosed cases, there was no significant difference between the remission cases and normal controls, nor difference between CCR AL patients and normal controls. All patients with high cyclin B1 expression had an unscheduled expression manner, that cyclin B1 protein appeared in G1 phase, and in some case it even higher than that of G2 phase.The response rate （partial remission ＋ complete remission） and survival rate in the cyclin B1 high expressed patients were higher than that of cyclin B1 low expressed patients. The relapse rate in cyclin B1 high expressed patients was higher than that in cyclin B1 normally expressed patients. The survival rate in cyclin B1 high expressed patients was higher than that in cyclin B1 low expression patients. A negative correlation between the expression of cyclin B1 and p21^cipl was observed. Additionally, cyclin B1 protein expression was generally correlated with proliferation index （PI）and proliferation cell nuclear antigen （PCNA）. It is concluded that this study demonstrates for the first time cyclin B1 overexpression and abnormally distribution in cell cyclin of newly diagnosed AL patients. It was considered that cyclin B1 may play an important role in leukemic pathogeneses and can be one of the factors influencing the prognosis of AL patients.