Shi Jun, Shao Zong-hong, Liu Hong, Jia Hai-rong, Sun Juan, Bai Jie, Cao Yan-ran, Wang Xiu-li, Tu Mei-feng
Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2005 Jan;26(1):10-4.
To study aberrant expression of cell cycle control genes in patients with myelodysplastic syndromes (MDS).
Reverse transcription polymerase chain reaction (RT-PCR) was used to investigate the expression of cell cycle control genes (cyclin D2, cyclin D3, cyclin A1, cyclin E, CDK2, CDK4, CDK6, p21, p27, p57, Rb and E2F1) in bone marrow mononuclear cells (BMMNCs) from 29 normal control, 27 MDS and 19 de novo acute myeloid leukemia (AML).
The expression levels of cyclin D3 (0.65 +/- 0.17, P < 0.05) and cyclin A1 (0.48 +/- 0.04, P < 0.05) in MDS were higher than those in normal control and significantly lower than those in AML. The expression rates and levels of cyclin D2 (40.7% and 0.78 +/- 0.21) and cyclin E (51.9% and 0.52 +/- 0.10) in MDS were statistically higher than those in normal control and AML. The expression level of CDK2 in MDS (0.66 +/- 0.19, P < 0.01) was higher than that in normal control (0.42 +/- 0.04) and the expression rate of CDK6 in MDS (25.9%) higher than in normal control (3.4%, P < 0.05). There was no significant difference of the expression rates and levels of CDK4 in MDS, AML and normal control. The expression rates and levels of p21 (77.8% and 1.18 +/- 0.21) and p27 (48.1% and 1.14 +/- 0.40) in MDS were statistically higher than those in normal control and AML. The expression level of p57 in MDS (0.69 +/- 0.06) was higher than that (0.53 +/- 0.05, P < 0.01) in normal control but lower than in AML (0.96 +/- 0.16, P < 0.01). The expression rate (55.6%) and level (0.85 +/- 0.17) of Rb in MDS were significantly higher than those in normal control and AML. The expression rate (7.4%) and level (0.39 +/- 0.04) of E2F1 in MDS were comparable to those in normal control but lower than those in AML.
MDS clones have aberrant mechanism of cell cycle control: high expressions of cyclin family members, CDK2 and CDK6 may lead to high proliferation; high expression of p21 and p27 may cause the G1 phase arrest.
研究骨髓增生异常综合征(MDS)患者细胞周期调控基因的异常表达。
采用逆转录聚合酶链反应(RT-PCR)检测29例正常对照、27例MDS患者及19例初发急性髓系白血病(AML)患者骨髓单个核细胞(BMMNCs)中细胞周期调控基因(细胞周期蛋白D2、细胞周期蛋白D3、细胞周期蛋白A1、细胞周期蛋白E、周期蛋白依赖性激酶2、周期蛋白依赖性激酶4、周期蛋白依赖性激酶6、p21、p27、p57、视网膜母细胞瘤蛋白和E2F1)的表达。
MDS患者中细胞周期蛋白D3(0.65±0.17,P<0.05)和细胞周期蛋白A1(0.48±0.04,P<0.05)的表达水平高于正常对照,显著低于AML患者。MDS患者中细胞周期蛋白D2(40.7%和0.78±0.21)和细胞周期蛋白E(51.9%和0.52±0.10)的表达率和水平在统计学上高于正常对照和AML患者。MDS患者中周期蛋白依赖性激酶2的表达水平(0.66±0.19,P<0.01)高于正常对照(0.42±0.04),周期蛋白依赖性激酶6在MDS患者中的表达率(25.9%)高于正常对照(3.4%,P<0.05)。MDS、AML和正常对照中周期蛋白依赖性激酶4的表达率和水平无显著差异。MDS患者中p21(77.8%和1.18±0.21)和p27(48.1%和1.14±0.40)的表达率和水平在统计学上高于正常对照和AML患者。MDS患者中p57的表达水平(0.69±0.06)高于正常对照(0.53±0.05,P<0.01),但低于AML患者(0.96±0.16,P<0.01)。MDS患者中视网膜母细胞瘤蛋白的表达率(55.6%)和水平(0.85±0.17)显著高于正常对照和AML患者。MDS患者中E2F1的表达率(7.4%)和水平(0.39±0.04)与正常对照相当,但低于AML患者。
MDS克隆具有异常的细胞周期调控机制:细胞周期蛋白家族成员、周期蛋白依赖性激酶2和周期蛋白依赖性激酶6的高表达可能导致高增殖;p21和p27的高表达可能导致G1期阻滞。