Nakamaki Tsuyoshi, Hamano Yasuharu, Hisatake Jun-Ichi, Yokoyama Akihiro, Kawakami Kei-Ichiro, Tomoyasu Shigeru, Honma Yoshio, Koeffler Phillip
Department of Haematology, Showa University School of Medicine, Tokyo Department of Chemotherapy, Saitama Cancer Centre Research Institute, Saitama, Japan.
Br J Haematol. 2003 Oct;123(1):72-80. doi: 10.1046/j.1365-2141.2003.04569.x.
Cyclin A (A2) and cyclin A1 are members of the G2 cyclins, which are involved in the control of G2/M and G1/S transitions as well as mitosis. Human cyclin A1 was cloned as an A-type cyclin that is highly expressed in acute myeloid leukaemia (AML). The clinical significance of these cyclins in myeloid leukaemia remains to be clarified. We investigated the relative levels of these transcripts in 80 patients with de novo AML. Correlations with clinical parameters showed that the initial white blood cell count and serum lactate dehydrogenase levels were inversely associated with cyclin A (A2) mRNA levels (r = -0.276, P = 0.019) and cyclin A1 mRNA levels (r = -0.241, P = 0.042) respectively. They were independently associated with increased overall survival [P = 0.035 for cyclin A (A2) and P = 0.016 for cyclin A1]. Multivariate analysis using Cox's proportional hazard model showed that elevated cyclin A1 mRNA levels contributed significantly to the better prognosis of patients with AML. Furthermore, the analysis of survival probability showed that the group with high levels of both cyclin A (A2) and A1 survived significantly longer than the group with low expression of both these cyclins (P = 0.002). These data indicate that high expression levels of both cyclin A (A2) and A1 are associated with good prognosis in AML patients.
细胞周期蛋白A(A2)和细胞周期蛋白A1是G2期细胞周期蛋白的成员,它们参与G2/M和G1/S期转换以及有丝分裂的调控。人细胞周期蛋白A1作为一种在急性髓系白血病(AML)中高表达的A型细胞周期蛋白被克隆出来。这些细胞周期蛋白在髓系白血病中的临床意义仍有待阐明。我们研究了80例初发AML患者中这些转录本的相对水平。与临床参数的相关性分析显示,初始白细胞计数和血清乳酸脱氢酶水平分别与细胞周期蛋白A(A2)mRNA水平呈负相关(r = -0.276,P = 0.019)以及与细胞周期蛋白A1 mRNA水平呈负相关(r = -0.241,P = 0.042)。它们分别与总生存期延长独立相关[细胞周期蛋白A(A2)的P = 0.035,细胞周期蛋白A1的P = 0.016]。使用Cox比例风险模型进行的多变量分析显示,细胞周期蛋白A1 mRNA水平升高对AML患者的较好预后有显著贡献。此外,生存概率分析表明,细胞周期蛋白A(A2)和A1水平均高的组比这两种细胞周期蛋白表达均低的组存活时间显著更长(P = 0.002)。这些数据表明,细胞周期蛋白A(A2)和A1的高表达水平与AML患者的良好预后相关。