Shi Jun, Shao Zong-hong, Liu Hong, Jia Hai-rong, Sun Juan, Bai Jie, Wu Yu-hong, Jing Li-ping, He Guang-sheng, Cao Yan-Ran, Wang Xiu-li, Tu Mei-feng, Hao Yu-shu, Yang Tian-ying
Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2004 Nov;25(11):641-4.
To study the characteristics of cell cycle and proliferation of CD34+ hematopoietic stem cells in patients with myelodysplastic syndromes (MDS).
Propidium iodide staining was used to examine cell cycle parameters (G(0)/G(1), S and G(2)/M) of bone marrow mononuclear cells (BMMNCs) while immunofluorescent double staining and FACS techniques were used to measure Ki67 expression in BM CD34+ cells from normal control, patients with MDS, acute myeloid leukemia preceded by MDS (MDS-AML) and primary AML.
There was a statistical up-tendency in G(0)/G(1) phase proportion of BMMNCs whereas a statistical down-tendency in S and G(2)/M phase proportions among normal control, MDS and primary AML. Compared to primary AML, MDS-AML had significantly higher ratios of S (P < 0.05), G(2)/M (P < 0.05) and S + G(2)/M (P < 0.05) phase cells while lower ratio of G(0)/G(1) phase cells (P < 0.05). The proportion of CD34+Ki67+ cells in MDS patients was significantly higher than that in normal control (P = 0.004). So were the percentages of CD34+Ki67+ cells in low-risk [(0.54 +/- 0.49)%, P < 0.05] and high-risk MDS patients [(1.69 +/- 1.66)%, P = 0.022]. Furthermore, there was statistical difference between low-risk and high-risk MDS (P < 0.05). Compared to normal control and primary AML, MDS-patients had the highest proportion of CD34+Ki67+ cells [(16.75 +/- 13.58)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS patients [(48.50 +/- 20.49)%] was significantly higher than that in normal control [(27.71 +/- 16.04)%, P < 0.01]. So were the low-risk [(51.85 +/- 21.80)%, P = 0.002] and high-risk MDS [(43.93 +/- 18.57)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS-AML patients [(60.92 +/- 30.12)%] was the highest, and was statistically higher than that in both normal control (P < 0.01) and primary AML patients [(17.01 +/- 15.93)%, P < 0.001]. The proportion of CD34+Ki67+ cells in Ki67+ cells in MDS patients [(4.91 +/- 4.68)%, P < 0.01] was significantly higher than that [(2.43 +/- 2.37)%] in normal controls. In the low-risk MDS group it was (4.11 +/- 3.94)%, (P > 0.05) and in high-risk MDS group it was (5.76 +/- 5.38)%, (P < 0.05).
High proportion of G(0)/G(1) cells and G(1) phase arrest occurred in MDS. High proliferation capacity of MDS clone, especially that derived from CD34+ cells, might play an important role in the clonal expansion, diseases deterioration and worse prognosis of MDS.
研究骨髓增生异常综合征(MDS)患者CD34+造血干细胞的细胞周期及增殖特征。
采用碘化丙啶染色检测骨髓单个核细胞(BMMNCs)的细胞周期参数(G(0)/G(1)、S和G(2)/M),同时运用免疫荧光双染色和流式细胞术检测正常对照、MDS患者、MDS转化的急性髓系白血病(MDS-AML)及原发性急性髓系白血病患者骨髓CD34+细胞中Ki67的表达。
正常对照、MDS及原发性急性髓系白血病患者的BMMNCs中G(0)/G(1)期比例呈统计学上升趋势,而S期和G(2)/M期比例呈统计学下降趋势。与原发性急性髓系白血病相比,MDS-AML的S期(P < 0.05)、G(2)/M期(P < 0.05)及S + G(2)/M期(P < 0.05)细胞比例显著更高,而G(0)/G(1)期细胞比例更低(P < 0.05)。MDS患者CD34+Ki67+细胞比例显著高于正常对照(P = 0.004)。低危MDS患者((0.54 ± 0.49)%, P < 0.05)和高危MDS患者((1.69 ± 1.66)%, P = 0.022)的CD34+Ki67+细胞百分比也是如此。此外,低危和高危MDS之间存在统计学差异(P < 0.05)。与正常对照和原发性急性髓系白血病相比,MDS患者的CD34+Ki67+细胞比例最高((16.75 ± 13.58)%, P < 0.05)。MDS患者CD34+细胞中CD34+Ki67+细胞比例((48.50 ± 20.49)%)显著高于正常对照((27.71 ± 16.04)%, P < 0.01)。低危MDS患者((51.85 ± 21.80)%, P = 0.002)和高危MDS患者((43.93 ± 18.57)%, P < 0.05)也是如此。MDS-AML患者CD34+细胞中CD34+Ki67+细胞比例((60.92 ± 30.12)%)最高,且在统计学上高于正常对照(P < 0.01)和原发性急性髓系白血病患者((17.01 ± 15.93)%, P < 0.001)。MDS患者Ki67+细胞中CD34+Ki67+细胞比例((4.91 ± 4.68)%, P < 0.01)显著高于正常对照((2.43 ± 2.37)%)。低危MDS组为(4.11 ± 3.94)%, (P > 0.05),高危MDS组为(5.76 ± 5.38)%, (P < 0.05)。
MDS中G(0)/G(1)期细胞比例高且出现G(1)期阻滞。MDS克隆,尤其是源自CD34+细胞的克隆,具有高增殖能力,这可能在MDS的克隆性扩增、疾病进展及不良预后中起重要作用。