组蛋白去甲基化酶赖氨酸特异性去甲基化酶1在急性白血病的表达及其临床意义

Expression of Histone Demethylase Lysine Specific Demethylase 1 in Acute Leukemia and Its Clinical Significance

本研究探讨组蛋白去甲基化酶赖氨酸特异性去甲基化酶1(lysine specific demethylase 1,LSD1)在急性白血病的表达及其临床意义。采用Western blot方法半定量检测LSD1在HL-60和SHI-1白血病细胞株、不同病情(初诊、完全缓解、复发)急性白血病(acute leukemia,AL)患者及非恶性血液病对照者骨髓单个核细胞的表达水平。随访收集AL患者的临床资料,分析LSD1表达与临床预后的关系。结果表明,HL-60细胞和SHI-1细胞LSD1均呈阳性高表达,LSD1相对含量(LSD1/β-actin灰度比)分别为4.647±3.840和1.628±0.185(n=4);72例AL患者LSD1表达程度差异较大,阳性率为56.9%(41/72),LSD1相对含量平均为1.053±1.976;17例非恶性血液病对照组LSD1阳性率为0%,LSD1相对含量为0.004±0.012。LSD1阳性率在急性髓系白血病(AML)或急性淋巴细胞白血病(ALL)患者初诊组(90.4%,77.8%)与难治/复发组(100%,100%)均高于完全缓解(CR)组(4.7%,0%)(p=0.000);LSD1相对含量在AML与ALL患者初诊组之间(1.177±1.646,1.275±1.845)、难治/复发组之间(2.050±2.470,4.107±3.676)或CR组之间(0.029±0.033,0.019±0.024)差异无统计学意义(p>0.05);AL患者LSD1阳性率在初诊组(84.6%)与难治/复发组(100%)均高于CR组(3.8%),LSD1相对含量在初诊组(1.274±1.760)、难治/复发组(3.359±3.319)及CR组(0.027±0.031)均高于对照组(p<0.01),其中难治/复发组高于初诊组与CR组(p<0.01),初诊组高于CR组(p<0.01)。结论:LSD1过高表达与AL难治/复发有关,其表达水平能反映AL患者的病情,可成为对AL预后有提示作用的生物学标志。

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.