Lin Xiu-Mei, Zhong Wen-Ting, Wang Chun-Li, Wang Shun-Qing
Department of Hematology, Guangzhou Medical College, Guangzhou, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2011 Dec;19(6):1348-52.
The aim of this study was to investigate the expression of histone demethylase lysine specific demethylase1 (LSD1) in patients with acute leukemia (AL) and its clinical significance. LSD1 protein expression level was detected by semi-quantitative Western blot in HL-60 and SHI-1 leukemia cell line, in bone marrow mononuclear cells of acute AL patients with different condition [new diagnosis, complete remission (CR) and relapse] and in patients with non malignant hematopathy (control). Clinical data of AL patient followed up was collected. The relationship of LSD1 expression level with clinical prognosis was analyzed. The results showed that in HL-60 and SHI-1 leukemia cell line, LSD1 expression was strong positive, relative amount (LSD1/β-actin gray level rate) was 4.647 ± 3.840 and 1.628 ± 0.185 (n = 4) respectively. In 72 AL patients, LSD1 expression levels were quite different. LSD1 positive rate was 56.9% (41/72), average relative amount was 1.053 ± 1.976. In 17 controls, LSD1 positive rate was 0%, relative amount was 0.004 ± 0.012. The LSD1 positive rate in newly diagnosed AML or ALL group (90.4%, 77.8%) and refractory/relapse AML or ALL group (100%, 100%) was higher than that in AML or ALL CR group (4.7%, 0%) (p = 0.000), relative amount of LSD1 showed no statistically difference between newly diagnosed AML and ALL groups (1.177 ± 1.646, 1.275 ± 1.845) or refractory/relapse group (2.050 ± 2.470, 4.107 ± 3.676) and CR group (0.029 ± 0.033, 0.019 ± 0.024) (p > 0.05). In all AL patients, LSD1 positive rate in newly diagnosed (84.6%) and refractory/relapse groups (100%) was higher than that in CR group (3.8%). LSD1 relative amount in newly diagnosed group (1.274 ± 1.760), refractory/relapse group (3.359 ± 3.319) and CR group (0.027 ± 0.031) was higher than that in control group (p < 0.01), and in refractory/relapse group was higher than that in newly diagnosed group and CR group (p < 0.01), in newly diagnosed group was higher than that in CR group (p < 0.01). It is concluded that overexpression of LSD1 is correlated with refractory or relapse in AL. LSD1 expression level can reflect disease status of AL patients and may be a predictive biomarker for unfavourable prognosis of AL.
本研究旨在探讨组蛋白去甲基化酶赖氨酸特异性去甲基化酶1(LSD1)在急性白血病(AL)患者中的表达及其临床意义。采用半定量蛋白质免疫印迹法检测HL-60和SHI-1白血病细胞系、不同病情[初诊、完全缓解(CR)和复发]的急性AL患者骨髓单个核细胞以及非恶性血液病患者(对照组)中LSD1蛋白表达水平。收集随访的AL患者临床资料,分析LSD1表达水平与临床预后的关系。结果显示,在HL-60和SHI-1白血病细胞系中,LSD1表达呈强阳性,相对含量(LSD1/β-肌动蛋白灰度比值)分别为4.647±3.840和1.628±0.185(n = 4)。72例AL患者中,LSD1表达水平差异较大。LSD1阳性率为56.9%(41/72),平均相对含量为1.053±1.976。17例对照组中,LSD1阳性率为0%,相对含量为0.004±0.012。初诊急性髓系白血病(AML)或急性淋巴细胞白血病(ALL)组(90.4%,77.8%)和难治/复发AML或ALL组(100%,100%)的LSD1阳性率高于AML或ALL CR组(4.7%,0%)(p = 0.000),LSD1相对含量在初诊AML组与ALL组(1.177±1.646,1.275±1.845)、难治/复发组(2.050±2.470,4.107±3.676)与CR组(0.029±0.033,0.019±0.024)之间差异无统计学意义(p>0.05)。所有AL患者中,初诊(84.6%)和难治/复发组(100%)的LSD1阳性率高于CR组(3.8%)。初诊组(1.274±1.760)、难治/复发组(3.359±3.319)和CR组(0.027±0.031)的LSD1相对含量高于对照组(p<0.01),难治/复发组高于初诊组和CR组(p<0.01),初诊组高于CR组(p<0.01)。结论:LSD1过表达与AL的难治或复发相关。LSD1表达水平可反映AL患者的疾病状态,可能是AL不良预后的预测生物标志物。