硫氧还蛋白还原酶在髓系白血病中的表达及其意义

Expression of thioredoxin reductase in myeloid leukemia and its significance

目的探讨硫氧还蛋白还原酶（TrxR）mRNA和蛋白表达与髓系白血病的关系。方法收集急性髓系白血病（AML）组20例及慢性髓系白血病（CML）组20例骨髓标本，并选取20名健康人骨髓作为健康对照组，选取人类非小细胞肺癌A549细胞作为阳性对照组。应用实时荧光定量PCR法检测TrxR的mRNA表达，应用Westernblot法检测TrxR的蛋白表达水平。结果AML组、CML组、阳性对照组和健康对照组中TrxRmRNA相对定量表达[中位数（四分位距）]分别为6．751（13．459）、4．321（11．389）、18．477（2．089）、1．045（0．467）；AML患者初发／复发组与完全缓解（CR）组分别为17．814±3．979、4．860±1．550；CML患者初发组与治疗组分别为19．552（5．758）、3．459（2．047）。AML组、CML组、阳性对照组较健康对照组TrxRmRNA的表达水平升高（H=43．978，P〈0．001）；AML患者初发／复发组、CR组、阳性对照组较健康对照组TrxRmRNA表达水平升高（F=246．793，P〈0．001），初发／复发组与阳性对照组之间差异无统计学意义（P〉0．05），初发／复发组较CR组、CR组较健康对照组TrxRmRNA表达均升高（均P〈0．05）；CML患者初发组、治疗组、阳性对照组较健康对照组TrxRmRNA表达升高（H=38．222，P〈0．001），初发组与阳性对照组之间差异无统计学意义（P〉0．05），但初发组较治疗组、治疗组较健康对照组TrxR表达均增高（均P〈0．05）；AML患者初发／复发组与CML患者初发组TrxR表达差异无统计学意义（P〉0．05）。AML组、CML组、阳性对照组和健康对照组中TrxR的蛋白表达量分别为0．679、0．606、0．877和0．095。结论TrxR在髓系白血病患者中基因和蛋白表达水平均上调，正常造血干细胞中低表达的TrXR在髓系白血病中高表达，治疗后TrxR表达降低，其可作为髓系白血病诊断、疗效及预后判断的指标之一。

Objective To explore the expression of thioredoxin reductase （TrxR） mRNA and protein, as well as the relationship between TrxR and myeloid leukemia. Methods Bone marrow samples from 20 acute myeloid leukemia （AML）, 20 chronic myeloid leukemia （CML）, and 20 healthy persons as normal control group were collected. The human non small cell lung cancer A549 cells were selected as the positive control group. The expression of TrxR mRNA was detected by real-time quantitative polymerase chain reaction. The expression of TrxR protein level was detected by Western blot. Results The relative quantitation expressions of TrxR mRNA were 6.751 （13.459）, 4.321 （11.389）, 18.477 （2.089）, 1.045 （0.467） in AML, CML, positive control and normal control group, were 17.814±3.979 and 4.860±1.550 in the primary diagnosed/relapse group and complete remission （CR） group of AML patients, and were 19.552 （5.758） and 3.459 （2.047） in the primary diagnosed and treatment group of CML patients. The expression levels of TrxR mRNA in AML, CML and positive control group were significantly higher than that in normal contro! group （H = 43.978, P 〈 0.001）. For AML patients, the expression levels of TrxR mRNA in the primary diagnosed/relapse group, CR, positive control group were significantly higher than that in normal control group （F = 246,793, P 〈 0.001）, and the difference between the primary diagnosed/relapse group and positive control group was no significant （P 〉 0.05）. The expression of TrxR mRNA were higher in the primary diagnosed/relapse group than that in CR group, and that in CR group than that in normal control group （both P 〈 0.05）. For CML patients, the expression levels of TrxR mRNA in the primary diagnosed, treatment, positive control group were significantly higher than that in normal controls （H = 38.222, P 〈 0.001）, the difference between that in the primary diagnosed and that in positive control group was no significant difference （P 〉 0.05）, but the expression of TrxR were significantly higher in the primary diagnosed group than that in treatment group, and that in treatment group than that in normal controls （both P 〈 0.05）. The expression of TrxR mRNA in the primary diagnosed/relapse group of AML and the primary diagnosed group of CML showed no significant difference （P 〉 0.05）. The positive levels of TrxR protein were 0.679, 0.606, 0.877 and 0.095 in AML, CML, positive control and normal control group. TrxR protein was highly expressed in myeloid leukemia patients. Conclusion The expression levels of TrxR mRNA and protein are increased in myeloid leukemia. The low expression of TrxR in normal hematopoietic stem cells is highly expressed in myeloid leukemia, and is downgraded after treatment, which may be used as one of the parameters to diagnosis, effect and prognosis of myeloid leukemia.