Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication

Increased expression of intracellular thioredoxin has been implicated in th e inhibition of apoptosis and in a decrease in the sensitivity of the malig nancies to drug-induced apoptosis. In the present studies, we analyzed expr ession of thioredoxin in samples from 28 children with T-cell acute lymphob lastic leukemia and analyzed their sensitivity toward inhibition of thiored oxin expression. Thioredoxin was expressed in variable amounts. Higher expr ession was associated with higher WBC counts. Exogenously added thioredoxin stimulated proliferation of clonogenic cells among the T-cell acute lympho blastic leukemia samples expressing relatively lower levels of intracellula r thioredoxin, whereas there was no effect on the clonogenic cells expressi ng high levels of thioredoxin. In addition, there was differential sensitiv ity of the leukemia clonogenic cells toward 1-methylpropyl 2-imidazolyl dis ulfide, an inhibitor of thioredoxin expression, as compared with normal hem atopoietic progenitors. This suggests the possibility of using this approac h for treatment. Because overexpression of thioredoxin is associated with r esistance to many anticancer drugs, the inhibition of thioredoxin expressio n may overcome this drug resistance and probably sensitize leukemia cells t o other chemotherapeutic agents.