Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.
Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.
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发表时间：
2001-10
期刊：
影响因子：
11.2
通讯作者：
L. Shao;M. Diccianni;T. Tanaka;R. Gribi;A. Yu;J. Pullen;B. Camitta;J. Yu
中科院分区：
文献类型：
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作者：
L. Shao;M. Diccianni;T. Tanaka;R. Gribi;A. Yu;J. Pullen;B. Camitta;J. Yu
细胞内硫氧还蛋白表达的增加与抑制细胞凋亡和降低肿瘤对药物诱导的细胞凋亡的敏感性有关。在本研究中，我们分析了28例儿童T细胞急性淋巴细胞白血病标本中硫氧还蛋白的表达，并分析了其对硫氧还蛋白表达抑制的敏感性。硫氧还蛋白以不同的量表达。高表达与高WBC计数相关。在细胞内硫氧还蛋白水平相对较低的T细胞急性淋巴细胞性白血病标本中，外源性加入硫氧还蛋白可促进克隆细胞的增殖，而对高水平硫氧还蛋白表达的克隆细胞则无影响。此外，与正常造血祖细胞相比，白血病克隆细胞对硫氧还蛋白表达抑制物1-甲丙基-2-咪唑基二硫化物具有不同的敏感性。这表明使用这种方法进行治疗的可能性。由于硫氧还蛋白的过度表达与许多抗癌药物的耐药性有关，抑制硫氧还蛋白的表达可能会克服这种耐药性，并可能使白血病细胞对其他化疗药物敏感。
Increased expression of intracellular thioredoxin has been implicated in the inhibition of apoptosis and in a decrease in the sensitivity of the malignancies to drug-induced apoptosis. In the present studies, we analyzed expression of thioredoxin in samples from 28 children with T-cell acute lymphoblastic leukemia and analyzed their sensitivity toward inhibition of thioredoxin expression. Thioredoxin was expressed in variable amounts. Higher expression was associated with higher WBC counts. Exogenously added thioredoxin stimulated proliferation of clonogenic cells among the T-cell acute lymphoblastic leukemia samples expressing relatively lower levels of intracellular thioredoxin, whereas there was no effect on the clonogenic cells expressing high levels of thioredoxin. In addition, there was differential sensitivity of the leukemia clonogenic cells toward 1-methylpropyl 2-imidazolyl disulfide, an inhibitor of thioredoxin expression, as compared with normal hematopoietic progenitors. This suggests the possibility of using this approach for treatment. Because overexpression of thioredoxin is associated with resistance to many anticancer drugs, the inhibition of thioredoxin expression may overcome this drug resistance and probably sensitize leukemia cells to other chemotherapeutic agents.