THIOREDOXIN IN ALL AND ITS THERAPEUTIC IMPLICATIONS

描述：（申请人摘要）

DESCRIPTION: (Applicant's Abstract) This is a biological correlative study with three major objectives: (i) to investigate the expression of thioredoxin in primary childhood T- and B- lineage acute lymphoblastic leukemia (ALL), (ii) to correlate overexpression of thioredoxin with clinical features and outcome, and (iii) to examine the possible exploitation of the altered expression for future development of therapeutic interventions. Recent studies suggest that thioredoxin may be a newly identified oncoprotein for human cancer and supports the thioredoxin redox system as a rational target for the development of drugs to selectively inhibit cancer. Through collaboration with one of the national reference laboratories, headed by Dr. Alice Yu of POG, UCSD Medical Center, the applicant will analyze the expression of thioredoxin in primary T- and B-lineage leukemia from ALL patients uniformly treated by POG protocols with the following specific aims: Specific Aim 1: To carry out a systematic analysis of the expression of thioredoxin in T- and B- lineage ALL and to test the hypothesis that expression of thioredoxin may be correlated with clinical features and outcome; Specific Aim 2: To determine the plasma level of extracellular thioredoxin in ALL patients and to test the hypothesis that high level of thioredoxin in the plasma may have clinical significance and Specific Aim 3: To determine the in vitro sensitivity of primary ALL cells to 1-methylpropyldisulfide and other related compounds, and to explore for their anti-leukemic actions or induction of apoptosis. In order to develop future therapeutic reagents for leukemia, the effect of these disulfides on leukemia colony formation as well as normal hematopoiesis in vitro will also be studied.