Liu Bing-nan, Fu Rong, Wang Hua-quan, Li Li-juan, Yue Lan-zhu, Ruan Er-bao, Qu Wen, Liang Yong, Wang Guo-jin, Wang Xiao-ming, Liu Hong, Wu Yu-hong, Song Jia, Xing Li-min, Guan Jing, Wang Jun, Shao Zong-hong
Department of Hematology and Oncology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
Zhonghua Xue Ye Xue Za Zhi. 2012 Jun;33(6):480-3.
To investigate the expressions of STAT5 phosphorylation in CD34(+)CD38(-)CD123(+) bone marrow cells of the patients with myelodysplastic syndromes (MDS), and then evaluate the level of activation of STAT5 associated with cell proliferation in MDS clone cells.
The bone marrow mononuclear cells (BMMNC) were extracted from 36 MDS patients and 14 normal controls. The mean fluorescence intensities (MFI) of phosphorylated STAT5(P-STAT5) in CD34(+)CD38(-)CD123(+) and CD34(+)CD38(-)CD123(-)cells, with or without the stimulation of 10 U/ml EPO, were examined by flow cytometry (FCM).
Without stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 113.71 ± 67.22/173.05 ± 102.78, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (58.84 ± 27.51/68.99 ± 50.42, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (63.06 ± 21.06, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; With the EPO stimulation, the P-STAT5 MFI in CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients was 144.04 ± 58.11/239.45 ± 152.05, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (68.41 ± 25, 10/64.21 ± 23.43, P < 0.01) and the normal controls CD34(+)CD38(-)CD123(-) cells (75.21 ± 27.02, P < 0.01), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal control CD34(+)CD38(-)CD123(-) cells; The P-STAT5 MFI in the CD34(+)CD38(-)CD123(+) cells of low/high risk MDS patients with or without EPO stimulation were 21.80/28.86, which was significantly higher than that of CD34(+)CD38(-)CD123(-) cells (7.42/5.50, P < 0.01, P < 0.05) and the normal controls CD34(+)CD38(-)CD123(-) cells (6.39, P < 0.05), there was no significant difference between the CD34(+)CD38(-)CD123(-) cells of MDS patients and the normal controls CD34(+)CD38(-)CD123(-) cells; There was no significant difference of P-STAT5 MFI with or without EPO stimulation and the increased P-STAT5 MFI between the CD34(+)CD38(-)CD123(+) cells of low and high risk MDS.
STAT5 associated with cell proliferation was activated in CD34(+)CD38(-)CD123(+) bone marrow cells in MDS, which had more significant reactions to EPO than CD34(+)CD38(-)CD123(-) cells, indicating that CD34(+)CD38(-)CD123(+) bone marrow cells might be the real malignant MDS clone cells in MDS.
探讨骨髓增生异常综合征（MDS）患者CD34(+)CD38(-)CD123(+)骨髓细胞中信号转导和转录激活因子5（STAT5）磷酸化的表达情况，进而评估与MDS克隆细胞增殖相关的STAT5激活水平。
抽取36例MDS患者及14例正常对照者的骨髓单个核细胞（BMMNC）。采用流式细胞术（FCM）检测在有或无10 U/ml促红细胞生成素（EPO）刺激情况下，CD34(+)CD38(-)CD123(+)和CD34(+)CD38(-)CD123(-)细胞中磷酸化STAT5（P-STAT5）的平均荧光强度（MFI）。
未刺激时，低/高危MDS患者CD34(+)CD38(-)CD123(+)细胞中P-STAT5的MFI为113.71±67.22/173.05±102.78，显著高于CD34(+)CD38(-)CD123(-)细胞（58.84±27.51/68.99±50.42，P<0.01，P<0.05）以及正常对照CD34(+)CD38(-)CD123(-)细胞（63.06±21.06，P<0.05），MDS患者的CD34(+)CD38(-)CD123(-)细胞与正常对照CD34(+)CD38(-)CD123(-)细胞之间无显著差异；EPO刺激后，低/高危MDS患者CD34(+)CD38(-)CD123(+)细胞中P-STAT5的MFI为144.04±58.11/239.45±152.05，显著高于CD34(+)CD38(-)CD123(-)细胞（68.41±25.10/64.21±23.43，P<0.01）以及正常对照CD34(+)CD38(-)CD123(-)细胞（75.21±27.02，P<0.01），MDS患者的CD34(+)CD38(-)CD123(-)细胞与正常对照CD34(+)CD38(-)CD123(-)细胞之间无显著差异；低/高危MDS患者有或无EPO刺激时，CD34(+)CD38(-)CD123(+)细胞中P-STAT5的MFI升高分别为21.80/28.86，显著高于CD34(+)CD38(-)CD123(-)细胞（分别为7.42/5.50，P<0.01，P<0.05）以及正常对照CD34(+)CD38(-)CD123(-)细胞（6.39，P<0.05），MDS患者的CD34(+)CD38(-)CD123(-)细胞与正常对照CD34(+)CD38(-)CD123(-)细胞之间无显著差异；低危和高危MDS的CD34(+)CD38(-)CD123(+)细胞在有或无EPO刺激时P-STAT5的MFI及P-STAT5的MFI升高幅度均无显著差异。
MDS患者CD34(+)CD38(-)CD123(+)骨髓细胞中与细胞增殖相关的STAT5被激活，其对EPO的反应比CD34(+)CD38(-)CD123(-)细胞更显著，提示CD34(+)CD38(-)CD123(+)骨髓细胞可能是MDS中真正的恶性克隆细胞。
